fgf8a is the zebrafish orthologue of vertebrate FGF8 and one of two co-orthologues (with fgf8b) retained from the teleost-specific genome duplication; it is the gene mutated in acerebellar (ace). It encodes a secreted fibroblast growth factor of the FGF8/17/18 (FgfD) subfamily, with an N-terminal signal peptide and the FGF beta-trefoil core, that acts as an extracellular ligand for FGF receptor tyrosine kinases and activates Ras/MAPK signalling. Its spread through tissue is limited by endocytosis and lysosomal degradation in receiving cells, which shapes a signalling gradient. fgf8a is expressed from the blastula onward, in a dorsoventral gradient during gastrulation and later at the midbrain-hindbrain boundary, dorsal diencephalon, telencephalon, somites, tailbud, heart precursors, pharyngeal region, otic region and pectoral fin bud. It is required for the midbrain-hindbrain boundary (isthmic) organizer and cerebellum, for induction of myocardial precursors, for otic and epibranchial placode induction with fgf3, for Kupffer's vesicle ciliogenesis and left-right asymmetry, and it contributes to gastrula dorsoventral patterning, mesoderm formation and restriction of endoderm, somitic fast-muscle differentiation, hindbrain patterning, retinal patterning and pharyngeal pouch and cartilage development. Heterozygous adults show craniofacial skeletal defects. In zebrafish its paralogue fgf8b shares the midbrain-hindbrain boundary and somite expression domains but is not expressed during gastrulation or in the heart.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001708 cell fate specification | IGI PMID:12917294 Engrailed and Fgf8 act synergistically to maintain the bound... | KEEP AS NON CORE | Summary: Fgf8 keeps presumptive midbrain cells from adopting forebrain fate at the diencephalic-mesencephalic boundary. Reason: Scholpp et al. show that Fgf8 is necessary and sufficient to repress pax6.1 and that cells unable to receive an Fgf signal adopt forebrain fate; combined eng2/eng3 and fgf8 loss abolishes midbrain identity. Cell fate specification is a correct but generic readout of this organizer signal. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:12917294 cells in the presumptive midbrain neural plate require an Fgf signal to keep them from following a forebrain fate PMID:12917294 Combined loss of both Eng2/Eng3 and Fgf8 leads to complete loss of midbrain identity, resulting in fusion of the forebrain and the hindbrain primordia. |
| GO:0001708 cell fate specification | IGI PMID:12917294 Engrailed and Fgf8 act synergistically to maintain the bound... | KEEP AS NON CORE | Summary: Fgf8 keeps presumptive midbrain cells from adopting forebrain fate at the diencephalic-mesencephalic boundary. Reason: Scholpp et al. show that Fgf8 is necessary and sufficient to repress pax6.1 and that cells unable to receive an Fgf signal adopt forebrain fate; combined eng2/eng3 and fgf8 loss abolishes midbrain identity. Cell fate specification is a correct but generic readout of this organizer signal. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:12917294 cells in the presumptive midbrain neural plate require an Fgf signal to keep them from following a forebrain fate PMID:12917294 Combined loss of both Eng2/Eng3 and Fgf8 leads to complete loss of midbrain identity, resulting in fusion of the forebrain and the hindbrain primordia. |
| GO:0001708 cell fate specification | IMP PMID:12917294 Engrailed and Fgf8 act synergistically to maintain the bound... | KEEP AS NON CORE | Summary: Fgf8 keeps presumptive midbrain cells from adopting forebrain fate at the diencephalic-mesencephalic boundary. Reason: Scholpp et al. show that Fgf8 is necessary and sufficient to repress pax6.1 and that cells unable to receive an Fgf signal adopt forebrain fate; combined eng2/eng3 and fgf8 loss abolishes midbrain identity. Cell fate specification is a correct but generic readout of this organizer signal. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:12917294 cells in the presumptive midbrain neural plate require an Fgf signal to keep them from following a forebrain fate PMID:12917294 Combined loss of both Eng2/Eng3 and Fgf8 leads to complete loss of midbrain identity, resulting in fusion of the forebrain and the hindbrain primordia. |
| GO:0001756 somitogenesis | IGI PMID:14651930 Interplay between FGF, one-eyed pinhead, and T-box transcrip... | KEEP AS NON CORE | Summary: Zygotic oep;ace double mutants lack posterior tissues including somites. Reason: Griffin and Kimelman show that combined loss of Zoep and ace/fgf8 abolishes all posterior tissues. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:14651930 we show that Zoep and ace/fgf8 function are essential for the formation of all posterior tissues, including spinal cord. |
| GO:0003007 heart morphogenesis | IMP PMID:18639539 Reiterative roles for FGF signaling in the establishment of ... | KEEP AS NON CORE | Summary: fgf8 mutants have reduced heart size and altered chamber proportion. Reason: Marques et al. report heart size and chamber proportion defects in fgf8 mutants; FGF signalling acts in cardiac specification and later in ventricular growth. Heart morphogenesis is a downstream consequence of the cardiac progenitor role accepted under cardioblast differentiation. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:18639539 Heart size and chamber proportionality are both affected in zebrafish fgf8 mutants. |
| GO:0003208 cardiac ventricle morphogenesis | IMP PMID:10603341 Induction and differentiation of the zebrafish heart require... | KEEP AS NON CORE | Summary: ace mutants have a severely abnormal ventricle. Reason: Reifers et al. 2000 show the ventricle is particularly affected in ace mutants. The primary role is in myocardial precursor induction (accepted under cardioblast differentiation); ventricle morphogenesis is a downstream consequence. Supporting Evidence: PMID:10603341 In contrast, heart development, in particular of the ventricle, is severely abnormal in acerebellar mutants. PMID:10603341 These findings show that fgf8/acerebellar is required for induction and patterning of myocardial precursors. |
| GO:0005105 type 1 fibroblast growth factor receptor binding | IBA GO_REF:0000033 | ACCEPT | Summary: Binding of the secreted Fgf8 ligand to FGFR1 (type 1 FGF receptor). Reason: The PAINT node PTN007510376 covers the FGF8/17/18 (FgfD) clade, seeded by human FGF8, FGF17 and FGF18, whose receptor binding is experimentally established. fgf8a sits inside this clade and retains the FGF core domain; genetic and pharmacological FGFR inhibition phenocopies ace in several tissues, consistent with signalling through FGFRs. The IBA is sound for fgf8a, and equally for its paralogue fgf8b. Supporting Evidence: file:DANRE/fgf8a/fgf8a-uniprot.txt Plays an important role in the regulation of embryonic PMID:9609821 we show that acerebellar is a zebrafish Fgf8 mutation that may inactivate Fgf8 function |
| GO:0005111 type 2 fibroblast growth factor receptor binding | IBA GO_REF:0000033 | ACCEPT | Summary: Binding of the secreted Fgf8 ligand to FGFR2 (type 2 FGF receptor). Reason: The PAINT node PTN007510376 covers the FGF8/17/18 (FgfD) clade, seeded by human FGF8, FGF17 and FGF18, whose receptor binding is experimentally established. fgf8a sits inside this clade and retains the FGF core domain; genetic and pharmacological FGFR inhibition phenocopies ace in several tissues, consistent with signalling through FGFRs. The IBA is sound for fgf8a, and equally for its paralogue fgf8b. Supporting Evidence: file:DANRE/fgf8a/fgf8a-uniprot.txt Plays an important role in the regulation of embryonic PMID:9609821 we show that acerebellar is a zebrafish Fgf8 mutation that may inactivate Fgf8 function |
| GO:0005576 extracellular region | IBA GO_REF:0000033 | ACCEPT | Summary: fgf8a is a secreted ligand active in the extracellular region. Reason: fgf8a has an N-terminal signal peptide, and epitope-tagged Fgf8 spreads through extracellular space in the zebrafish neuroectoderm (PMID:15498491). The IBA is well founded. Supporting Evidence: file:DANRE/fgf8a/fgf8a-uniprot.txt SIGNAL 1..27 PMID:15498491 If internalization is inhibited, Fgf8 protein accumulates extracellularly, spreads further, and activates target gene expression over a greater distance. |
| GO:0005576 extracellular region | IDA PMID:15498491 Endocytosis controls spreading and effective signaling range... | ACCEPT | Summary: Tagged Fgf8 accumulates and spreads in the extracellular space of the neuroectoderm. Reason: Scholpp and Brand directly visualised extracellular Fgf8 protein and showed that its extracellular range sets its signalling range. This is the functional location of the ligand. Supporting Evidence: PMID:15498491 If internalization is inhibited, Fgf8 protein accumulates extracellularly, spreads further, and activates target gene expression over a greater distance. PMID:15498491 We find that spreading of epitope-tagged Fgf8 through target tissue is carefully controlled by endocytosis and subsequent degradation in lysosomes |
| GO:0005576 extracellular region | IEA GO_REF:0000044 | ACCEPT | Summary: Secreted (UniProt subcellular location mapping). Reason: Consistent with the signal peptide and with direct observation of extracellular Fgf8 (PMID:15498491). Supporting Evidence: file:DANRE/fgf8a/fgf8a-uniprot.txt SUBCELLULAR LOCATION: Secreted PMID:15498491 If internalization is inhibited, Fgf8 protein accumulates extracellularly, spreads further, and activates target gene expression over a greater distance. |
| GO:0005576 extracellular region | ISS GO_REF:0000024 | ACCEPT | Summary: Secreted, by similarity to human FGF8 (P55075). Reason: Transfer from human FGF8 is appropriate for the orthologue and is independently confirmed by zebrafish data (PMID:15498491). Supporting Evidence: file:DANRE/fgf8a/fgf8a-uniprot.txt SUBCELLULAR LOCATION: Secreted PMID:15498491 If internalization is inhibited, Fgf8 protein accumulates extracellularly, spreads further, and activates target gene expression over a greater distance. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Cytoplasm, propagated from the FGF family root node. Reason: The node PTN000160075 covers the whole FGF family, including non-secreted FGF1/FGF2 and intracellular FGFs. fgf8a has a signal peptide and acts as a secreted ligand; the only intracellular location with direct evidence is lysosomes of receiving cells after endocytic clearance (PMID:15498491), which is not a site of activity. This matches the treatment of the same IBA in the human FGF8 review. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN000160075 SUPPORTS SOURCE BUT NOT TARGET Family-level FGF node that includes intracellular and non-classically secreted FGFs (for example FGF1, FGF2); fgf8a has a signal peptide and acts extracellularly. Supporting Evidence: file:DANRE/fgf8a/fgf8a-uniprot.txt SIGNAL 1..27 PMID:15498491 We find that spreading of epitope-tagged Fgf8 through target tissue is carefully controlled by endocytosis and subsequent degradation in lysosomes |
| GO:0005764 lysosome | IDA PMID:15498491 Endocytosis controls spreading and effective signaling range... | KEEP AS NON CORE | Summary: Fgf8 protein is endocytosed by target cells and degraded in lysosomes. Reason: The IDA is correct: tagged Fgf8 is found in lysosomes after internalisation, and this restrictive clearance shapes the gradient. The lysosome is where the ligand is degraded, not where it acts, so the location is kept as non-core. Supporting Evidence: PMID:15498491 We find that spreading of epitope-tagged Fgf8 through target tissue is carefully controlled by endocytosis and subsequent degradation in lysosomes |
| GO:0007368 determination of left/right symmetry | IGI PMID:19481538 Fgf4 is required for left-right patterning of visceral organ... | ACCEPT | Summary: Left-right patterning, from combined fgf4/fgf8 knockdown. Reason: Yamauchi et al. focus on fgf4 but state the established fgf8 requirement for Kupffer's vesicle formation. Left-right determination is a well supported fgf8a role (PMID:15932752, PMID:19164561). Accepted, consistent with the IMP row. Supporting Evidence: PMID:19481538 Fgf8 is also known to be crucial for the formation of Kupffer's vesicle, which is needed for the LR patterning of visceral organs. PMID:15932752 We find that fgf8 is required for proper asymmetric development of the brain, heart and gut. |
| GO:0007368 determination of left/right symmetry | IMP PMID:15932752 Roles for fgf8 signaling in left-right patterning of the vis... | ACCEPT | Summary: ace/fgf8 mutants randomise brain, heart and gut laterality and often lack Kupffer's vesicle. Reason: Albertson and Yelick show fgf8 is required for asymmetric development of brain, heart and gut, with loss of Kupffer's vesicle in about a third of mutants; Hong and Dawid show KV cilia depend on Fgf8 (PMID:19164561). This is one of the best established fgf8a roles. Supporting Evidence: PMID:15932752 We find that fgf8 is required for proper asymmetric development of the brain, heart and gut. PMID:15932752 Approximately 1/3 of zebrafish ace/fgf8 mutants are missing Kupffer's vesicle (KV) |
| GO:0007420 brain development | IMP PMID:12843251 Genetic analysis of the roles of Hh, FGF8, and nodal signali... | KEEP AS NON CORE | Summary: ace mutants have brain defects including loss of locus coeruleus and anterior posterior-tuberculum DA neurons. Reason: Full text of Holzschuh et al. confirms brain defects in ace (MHB, cerebellum, LC and late DA neuron loss). Brain development is a correct but broad term; the specific MHB role is accepted separately. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:12843251 However, at 3 dpf, ace mutant embryos lack the most anterior DA neurons in the posterior tuberculum PMID:12843251 the lack-of-function ace phenotype indicates a role of FGF8 in NA neuron development in the locus coeruleus (LC) |
| GO:0007422 peripheral nervous system development | IGI PMID:17215310 Specification of epibranchial placodes in zebrafish. | KEEP AS NON CORE | Summary: fgf3/fgf8 are required for epibranchial placode induction (peripheral sensory ganglia). Reason: Nechiporuk et al. show fgf3;fgf8 double mutants/morphants do not express epibranchial placode markers. The role is shared with fgf3. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:17215310 zebrafish embryos mutant for fgf3 and fgf8 do not express early EB placode markers, including foxi1 and pax2a |
| GO:0007422 peripheral nervous system development | IGI PMID:17215310 Specification of epibranchial placodes in zebrafish. | KEEP AS NON CORE | Summary: fgf3/fgf8 are required for epibranchial placode induction (peripheral sensory ganglia). Reason: Nechiporuk et al. show fgf3;fgf8 double mutants/morphants do not express epibranchial placode markers. The role is shared with fgf3. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:17215310 zebrafish embryos mutant for fgf3 and fgf8 do not express early EB placode markers, including foxi1 and pax2a |
| GO:0007492 endoderm development | IDA PMID:17026981 Fgf signaling negatively regulates Nodal-dependent endoderm ... | MODIFY | Summary: Fgf signalling limits endoderm induction (IDA). Reason: Mizoguchi et al. show that Fgf activity negatively regulates endoderm induction via casanova. "Endoderm development" is a broad parent; the specific claim is already captured by negative regulation of endodermal cell fate specification (GO:0042664), which fgf8a also carries from PMID:16672336. Proposed replacements: negative regulation of endodermal cell fate specification Supporting Evidence: PMID:17026981 Fgf signaling negatively regulates endoderm induction, possibly through repression of cas expression and down-regulation of Cas function |
| GO:0007492 endoderm development | IMP PMID:15509770 An essential role for Fgfs in endodermal pouch formation inf... | KEEP AS NON CORE | Summary: ace mutants with reduced fgf3 fail to form pharyngeal endodermal pouches. Reason: Crump et al. show Fgf8 and Fgf3 are required for pharyngeal pouch formation by endoderm. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:15509770 In animals doubly reduced for Fgf8 and Fgf3, the migration of pharyngeal endodermal cells is disorganized and pouches fail to form. |
| GO:0007498 mesoderm development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Mesoderm development (ARBA machine-learning inference). Reason: Supported for fgf8a by direct genetic evidence: ace;oep double mutants lose mesoderm (PMID:14711879, PMID:14651930). Kept as non-core, like the experimental rows for the same term. Supporting Evidence: PMID:14711879 combining zygotic mutations in ace/fgf8 and oep disrupts mesoderm formation, a phenotype that is not produced by either mutation alone |
| GO:0007498 mesoderm development | IGI PMID:14651930 Interplay between FGF, one-eyed pinhead, and T-box transcrip... | KEEP AS NON CORE | Summary: Zoep;ace double mutants lose posterior mesoderm. Reason: Genetic interaction evidence from Griffin and Kimelman. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:14651930 we show that Zoep and ace/fgf8 function are essential for the formation of all posterior tissues, including spinal cord. |
| GO:0007498 mesoderm development | IGI PMID:14711879 Nodal and Fgf pathways interact through a positive regulator... | KEEP AS NON CORE | Summary: ace and oep synergise in mesoderm formation. Reason: Mathieu et al. show combined zygotic loss of ace/fgf8 and oep disrupts mesoderm, which neither single mutation does. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:14711879 combining zygotic mutations in ace/fgf8 and oep disrupts mesoderm formation, a phenotype that is not produced by either mutation alone |
| GO:0007498 mesoderm development | IGI PMID:14711879 Nodal and Fgf pathways interact through a positive regulator... | KEEP AS NON CORE | Summary: ace and oep synergise in mesoderm formation. Reason: Mathieu et al. show combined zygotic loss of ace/fgf8 and oep disrupts mesoderm, which neither single mutation does. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:14711879 combining zygotic mutations in ace/fgf8 and oep disrupts mesoderm formation, a phenotype that is not produced by either mutation alone |
| GO:0008083 growth factor activity | IBA GO_REF:0000033 | ACCEPT | Summary: Growth factor activity (FGF family IBA). Reason: fgf8a is a canonical secreted FGF ligand; misexpression dorsalises embryos, induces ectopic otic tissue and rescues ace phenotypes (PMID:9609821, PMID:14757644, PMID:10603341). Core molecular function. Supporting Evidence: PMID:9609821 we show that acerebellar is a zebrafish Fgf8 mutation that may inactivate Fgf8 function file:DANRE/fgf8a/fgf8a-uniprot.txt Plays an important role in the regulation of embryonic |
| GO:0008083 growth factor activity | IEA GO_REF:0000002 | ACCEPT | Summary: Growth factor activity (InterPro FGF family mapping). Reason: Consistent with the IBA and with experimental data. Supporting Evidence: file:DANRE/fgf8a/fgf8a-uniprot.txt Plays an important role in the regulation of embryonic |
| GO:0008284 positive regulation of cell population proliferation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Positive regulation of cell population proliferation (FGF family IBA). Reason: FGFs are mitogens and Fgf8 is required for proliferation of the cerebellar territory (PMID:16611693). Kept as non-core, as in the human FGF8 review. Supporting Evidence: PMID:16611693 Fgf8 is not instructive in establishing zebrafish cerebellar cell identities, although it is required for proliferation and morphogenesis of this territory |
| GO:0008543 fibroblast growth factor receptor signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: FGF receptor signaling pathway (IBA). Reason: Core process for a FGF ligand; Fgf8 activates Ras/MAPK target genes (sef, pea3) and its loss is phenocopied by FGFR inhibition in many zebrafish tissues. Supporting Evidence: PMID:11802165 FGFs regulate dorsoventral patterning by controlling ventral bone morphogenetic protein (BMP) expression. file:DANRE/fgf8a/fgf8a-uniprot.txt Plays an important role in the regulation of embryonic |
| GO:0009880 embryonic pattern specification | IGI PMID:16873584 FGF signaling is required for {beta}-catenin-mediated induct... | KEEP AS NON CORE | Summary: FGF signalling is required downstream of beta-catenin/squint for organizer gene expression. Reason: Maegawa et al. show FGF signalling is needed for beta-catenin induction of the organizer. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:16873584 These results demonstrate that FGF signaling is necessary for beta-catenin induction of the zebrafish organizer. |
| GO:0009887 animal organ morphogenesis | IMP PMID:15932752 Roles for fgf8 signaling in left-right patterning of the vis... | KEEP AS NON CORE | Summary: ace mutants show left-right defects in visceral organ and pharyngeal skeleton morphogenesis. Reason: Animal organ morphogenesis is a broad grouping term for the laterality defects of brain, heart and gut in ace (accepted more specifically as determination of left/right symmetry). Supporting Evidence: PMID:15932752 We find that fgf8 is required for proper asymmetric development of the brain, heart and gut. |
| GO:0009952 anterior/posterior pattern specification | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Anterior/posterior pattern specification (ARBA). Reason: Supported for fgf8a by experimental evidence on midbrain/forebrain boundary positioning and hindbrain patterning (PMID:12917294, PMID:14745965). Kept as non-core, like the experimental rows for the same term. Supporting Evidence: PMID:12917294 Combined loss of both Eng2/Eng3 and Fgf8 leads to complete loss of midbrain identity, resulting in fusion of the forebrain and the hindbrain primordia. PMID:14745965 These data demonstrate an early, nonredundant requirement for fgf8 function in hindbrain patterning. |
| GO:0009952 anterior/posterior pattern specification | IGI PMID:12917294 Engrailed and Fgf8 act synergistically to maintain the bound... | KEEP AS NON CORE | Summary: Fgf8 positions the diencephalic-mesencephalic boundary along the A/P axis. Reason: Scholpp et al.: Fgf8 represses pax6.1 and shifts the DMB anteriorly; with eng2/eng3 it maintains midbrain identity. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:12917294 Combined loss of both Eng2/Eng3 and Fgf8 leads to complete loss of midbrain identity, resulting in fusion of the forebrain and the hindbrain primordia. PMID:12917294 cells in the presumptive midbrain neural plate require an Fgf signal to keep them from following a forebrain fate |
| GO:0009952 anterior/posterior pattern specification | IGI PMID:12917294 Engrailed and Fgf8 act synergistically to maintain the bound... | KEEP AS NON CORE | Summary: Fgf8 positions the diencephalic-mesencephalic boundary along the A/P axis. Reason: Scholpp et al.: Fgf8 represses pax6.1 and shifts the DMB anteriorly; with eng2/eng3 it maintains midbrain identity. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:12917294 Combined loss of both Eng2/Eng3 and Fgf8 leads to complete loss of midbrain identity, resulting in fusion of the forebrain and the hindbrain primordia. PMID:12917294 cells in the presumptive midbrain neural plate require an Fgf signal to keep them from following a forebrain fate |
| GO:0009952 anterior/posterior pattern specification | IGI PMID:15342476 vhnf1 integrates global RA patterning and local FGF signals ... | KEEP AS NON CORE | Summary: Fgf signals from r4 act with vhnf1 in caudal hindbrain A/P patterning. Reason: Hernandez et al. show Fgf from r4 cooperates with Vhnf1 to specify r5/r6. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:15342476 Fgf signals from r4, acting through the MapK pathway, then cooperate with Vhnf1 to activate val expression and subsequent r5 and r6 development. |
| GO:0009952 anterior/posterior pattern specification | IMP PMID:12917294 Engrailed and Fgf8 act synergistically to maintain the bound... | KEEP AS NON CORE | Summary: Fgf8 positions the diencephalic-mesencephalic boundary along the A/P axis. Reason: Scholpp et al.: Fgf8 represses pax6.1 and shifts the DMB anteriorly; with eng2/eng3 it maintains midbrain identity. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:12917294 Combined loss of both Eng2/Eng3 and Fgf8 leads to complete loss of midbrain identity, resulting in fusion of the forebrain and the hindbrain primordia. PMID:12917294 cells in the presumptive midbrain neural plate require an Fgf signal to keep them from following a forebrain fate |
| GO:0009953 dorsal/ventral pattern formation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Dorsal/ventral pattern formation (IBA, FgfD node). Reason: The node PTN002608342 is seeded by zebrafish fgf8a and fgf24 and by mouse Fgf8. fgf8a is expressed in a dorsoventral gradient during gastrulation and its loss enhances chordin ventralisation (PMID:9609821, PMID:15151985), so the IBA is right for fgf8a. Non-core as for human FGF8. Supporting Evidence: PMID:15151985 we show that loss of Fgf8 function enhances the ventralisation of chordin-deficient embryos |
| GO:0009953 dorsal/ventral pattern formation | IDA PMID:16890217 Noggin1 and Follistatin-like2 function redundantly to Chordi... | KEEP AS NON CORE | Summary: D/V axis patterning (IDA, from a noggin/follistatin-like paper). Reason: The cached abstract of PMID:16890217 does not mention fgf8, but D/V patterning by fgf8a is established (PMID:15151985, PMID:9609821). Deferring to the curator, who read the full text. Supporting Evidence: PMID:15151985 we show that loss of Fgf8 function enhances the ventralisation of chordin-deficient embryos |
| GO:0009953 dorsal/ventral pattern formation | IGI PMID:15151985 Fgf signalling controls the dorsoventral patterning of the z... | KEEP AS NON CORE | Summary: Loss of Fgf8 enhances the ventralisation of chordin mutants. Reason: Furthauer et al. show pre-gastrula Fgf signalling restricts bmp expression and that loss of Fgf8 function enhances chordin ventralisation. Gastrula D/V patterning is a well established fgf8a role, and one that the paralogue fgf8b cannot share in vivo because it is not expressed during gastrulation (PMID:11091072). Kept as non-core, consistent with the other rows for this term and with the human FGF8 review. Kept as non-core, consistent with the other rows for this term and with the human FGF8 review. Supporting Evidence: PMID:15151985 we show that loss of Fgf8 function enhances the ventralisation of chordin-deficient embryos PMID:11091072 fgf17 can act similar to fgf8 during gastrulation, when fgf17 is not normally expressed |
| GO:0009953 dorsal/ventral pattern formation | IMP PMID:11802165 Sef is a feedback-induced antagonist of Ras/MAPK-mediated FG... | KEEP AS NON CORE | Summary: D/V patterning, from the Sef paper. Reason: Furthauer et al. 2002 describe FGF regulation of ventral BMP expression and Sef as a feedback antagonist of Fgf8 signalling. Consistent with the accepted D/V role. Supporting Evidence: PMID:11802165 FGFs regulate dorsoventral patterning by controlling ventral bone morphogenetic protein (BMP) expression. |
| GO:0009953 dorsal/ventral pattern formation | IMP PMID:15151985 Fgf signalling controls the dorsoventral patterning of the z... | KEEP AS NON CORE | Summary: Loss of Fgf8 enhances the ventralisation of chordin mutants. Reason: Furthauer et al. show pre-gastrula Fgf signalling restricts bmp expression and that loss of Fgf8 function enhances chordin ventralisation. Gastrula D/V patterning is a well established fgf8a role, and one that the paralogue fgf8b cannot share in vivo because it is not expressed during gastrulation (PMID:11091072). Kept as non-core, consistent with the other rows for this term and with the human FGF8 review. Kept as non-core, consistent with the other rows for this term and with the human FGF8 review. Supporting Evidence: PMID:15151985 we show that loss of Fgf8 function enhances the ventralisation of chordin-deficient embryos PMID:11091072 fgf17 can act similar to fgf8 during gastrulation, when fgf17 is not normally expressed |
| GO:0010002 cardioblast differentiation | IMP PMID:10603341 Induction and differentiation of the zebrafish heart require... | ACCEPT | Summary: fgf8 is required for initiation of nkx2.5 and gata4 in cardiac precursors. Reason: Reifers et al. 2000 show fgf8 is expressed in and required for heart precursors, with rescue by fgf8 RNA or Fgf8 beads. In zebrafish this cardiac role belongs to fgf8a only: fgf8b is not expressed in the heart (PMID:19562753). Supporting Evidence: PMID:10603341 These findings show that fgf8/acerebellar is required for induction and patterning of myocardial precursors. |
| GO:0014709 positive regulation of somitomeric trunk muscle development | IMP PMID:16120642 Fgf8 drives myogenic progression of a novel lateral fast mus... | KEEP AS NON CORE | Summary: Fgf8 drives terminal differentiation of lateral fast muscle. Reason: Groves et al. show Fgf8 signalling in the somite is required for myod expression and differentiation of lateral fast muscle fibres. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:16120642 we show that Fgf8 signalling in the somite is required for myod expression and terminal differentiation of a subset of fast muscle cells in the zebrafish lateral somite |
| GO:0021549 cerebellum development | IMP PMID:22223680 Midbrain-hindbrain boundary patterning and morphogenesis are... | ACCEPT | Summary: Cerebellum development (fgf8 morphants, grhl2b paper). Reason: Cerebellum development is the defining ace phenotype (PMID:9609821, PMID:9007239); the curator of PMID:22223680 recorded it from fgf8 morphants. Supporting Evidence: PMID:22223680 Formation and maintenance of the MHB is characterised by a hierarchical program of gene expression initiated by fibroblast growth factor 8 (Fgf8) PMID:9609821 Homozygous acerebellar embryos lack a cerebellum and the midbrain-hindbrain boundary organizer. |
| GO:0021555 midbrain-hindbrain boundary morphogenesis | IGI PMID:22223680 Midbrain-hindbrain boundary patterning and morphogenesis are... | ACCEPT | Summary: MHB morphogenesis, genetic interaction of fgf8 and grhl2b. Reason: Dworkin et al. place Fgf8 at the top of the MHB gene-expression hierarchy; the IGI records its interaction with grhl2b in MHB folding. Consistent with the core MHB organizer role. Supporting Evidence: PMID:22223680 Formation and maintenance of the MHB is characterised by a hierarchical program of gene expression initiated by fibroblast growth factor 8 (Fgf8) |
| GO:0021571 rhombomere 5 development | IGI PMID:12835397 vhnf1 and Fgf signals synergize to specify rhombomere identi... | KEEP AS NON CORE | Summary: Fgf signals synergise with vhnf1 to specify rhombomeres 5 and 6. Reason: Wiellette and Sive show vhnf1 acts in obligate synergy with Fgf signals in r5/r6 specification. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:12835397 vhnf1 promotes r5+r6 identity through an obligate synergy with Fgf signals to activate valentino and krox20 expression |
| GO:0021572 rhombomere 6 development | IGI PMID:12835397 vhnf1 and Fgf signals synergize to specify rhombomere identi... | KEEP AS NON CORE | Summary: Fgf signals synergise with vhnf1 to specify rhombomeres 5 and 6. Reason: Wiellette and Sive show vhnf1 acts in obligate synergy with Fgf signals in r5/r6 specification. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:12835397 vhnf1 promotes r5+r6 identity through an obligate synergy with Fgf signals to activate valentino and krox20 expression |
| GO:0021588 cerebellum formation | IMP PMID:12591239 Wnt1 and wnt10b function redundantly at the zebrafish midbra... | ACCEPT | Summary: ace mutants lack a cerebellum; wnt1/wnt10b-deficient embryos are sensitised to loss of Fgf8. Reason: Loss of the cerebellum is the defining acerebellar phenotype. Supporting Evidence: PMID:9609821 Homozygous acerebellar embryos lack a cerebellum and the midbrain-hindbrain boundary organizer. PMID:12591239 Embryos homozygous for the wnt1-wnt10b deficiency display a mild MHB phenotype, but are sensitized to reductions in either Pax2.1 or Fgf8; that is, in combination with mutant alleles of either of these loci, the morphological MHB is lost. |
| GO:0021703 locus ceruleus development | IGI PMID:17215310 Specification of epibranchial placodes in zebrafish. | KEEP AS NON CORE | Summary: Locus coeruleus, from fgf3/fgf8 knockdown in the epibranchial placode paper. Reason: The cached abstract does not mention the LC, but the absence of the LC in ace mutants is independently established (PMID:12843251, PMID:10595509). Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:12843251 the lack-of-function ace phenotype indicates a role of FGF8 in NA neuron development in the locus coeruleus (LC) |
| GO:0021703 locus ceruleus development | IMP PMID:10595509 Development of noradrenergic neurons in the zebrafish hindbr... | KEEP AS NON CORE | Summary: Phox2a in LC progenitors depends on Fgf8 from the MHB. Reason: Guo et al. show LC specification depends on FGF8 from the MHB. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:10595509 its expression there is dependent on FGF8 from the mid/hindbrain boundary PMID:12843251 the lack-of-function ace phenotype indicates a role of FGF8 in NA neuron development in the locus coeruleus (LC) |
| GO:0022008 neurogenesis | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Neurogenesis (FGF family IBA). Reason: Correct in outline (MHB organizer, LC and 5HT neuron development) but broad; non-core as for human FGF8. Supporting Evidence: PMID:15281067 Hindbrain 5HT neurons are severely reduced in mutants lacking activity of either Ace/Fgf8 or the transcription factor Noi/Pax2.1 |
| GO:0030177 positive regulation of Wnt signaling pathway | IGI PMID:14757644 A direct role for Fgf but not Wnt in otic placode induction. | UNDECIDED | Summary: Positive regulation of Wnt signaling (IGI with fgf3). Reason: The cached abstract of Phillips et al. describes the reverse relationship: Wnt8 regulates the timely expression of fgf3 and fgf8 in the hindbrain, and Fgf, not Wnt, acts on preotic cells. I cannot see the result on which the curator based an Fgf8-upstream-of-Wnt annotation, so I neither accept nor remove it. Supporting Evidence: PMID:14757644 We propose that Wnt8 serves to regulate timely expression of Fgf3 and Fgf8 in the hindbrain, and that Fgf from the hindbrain then acts directly on preplacodal cells to induce otic differentiation. |
| GO:0030182 neuron differentiation | IMP PMID:12843251 Genetic analysis of the roles of Hh, FGF8, and nodal signali... | KEEP AS NON CORE | Summary: ace mutants lose LC noradrenergic neurons and late anterior DA neurons. Reason: Full text of Holzschuh et al.: Fgf8 is not needed to specify the earliest DA neurons, but ace mutants lack LC neurons and later lose anterior posterior-tuberculum DA neurons. Neuron differentiation is a correct broad readout. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:12843251 the lack-of-function ace phenotype indicates a role of FGF8 in NA neuron development in the locus coeruleus (LC) PMID:12843251 However, at 3 dpf, ace mutant embryos lack the most anterior DA neurons in the posterior tuberculum |
| GO:0030334 regulation of cell migration | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Regulation of cell migration (FGF family IBA). Reason: Supported in zebrafish: Fgf8a acts as a guidance cue for migrating pharyngeal pouch cells (PMID:25142463). Non-core. Supporting Evidence: PMID:25142463 Fgf8a acts as a Wnt11r-dependent guidance cue for migrating pouch cells |
| GO:0030335 positive regulation of cell migration | IGI PMID:15509770 An essential role for Fgfs in endodermal pouch formation inf... | KEEP AS NON CORE | Summary: Fgf8 with fgf3 directs lateral migration of pharyngeal endoderm. Reason: Crump et al. show that endodermal cell migration is disorganised when Fgf8 and Fgf3 are reduced; Choe and Crump later identify Fgf8a as a guidance cue for pouch cells. Supporting Evidence: PMID:15509770 In animals doubly reduced for Fgf8 and Fgf3, the migration of pharyngeal endodermal cells is disorganized and pouches fail to form. PMID:25142463 Fgf8a acts as a Wnt11r-dependent guidance cue for migrating pouch cells |
| GO:0030878 thyroid gland development | IMP PMID:17611226 Early developmental specification of the thyroid gland depen... | KEEP AS NON CORE | Summary: ace mutants have thyroid defects. Reason: Wendl et al. report thyroid defects in ace mutants like those of hand2 mutants, with FGF acting from surrounding tissue. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:17611226 The zebrafish ace (fgf8) mutant has similar thyroid defects as han mutants |
| GO:0030901 midbrain development | IGI PMID:12917294 Engrailed and Fgf8 act synergistically to maintain the bound... | ACCEPT | Summary: Fgf8 maintains midbrain identity and positions the diencephalic-mesencephalic boundary. Reason: Scholpp et al.: combined loss of Eng2/Eng3 and Fgf8 abolishes midbrain identity. Midbrain patterning is part of the MHB organizer function that defines fgf8a. Supporting Evidence: PMID:12917294 Combined loss of both Eng2/Eng3 and Fgf8 leads to complete loss of midbrain identity, resulting in fusion of the forebrain and the hindbrain primordia. PMID:12917294 cells in the presumptive midbrain neural plate require an Fgf signal to keep them from following a forebrain fate |
| GO:0030901 midbrain development | IGI PMID:12917294 Engrailed and Fgf8 act synergistically to maintain the bound... | ACCEPT | Summary: Fgf8 maintains midbrain identity and positions the diencephalic-mesencephalic boundary. Reason: Scholpp et al.: combined loss of Eng2/Eng3 and Fgf8 abolishes midbrain identity. Midbrain patterning is part of the MHB organizer function that defines fgf8a. Supporting Evidence: PMID:12917294 Combined loss of both Eng2/Eng3 and Fgf8 leads to complete loss of midbrain identity, resulting in fusion of the forebrain and the hindbrain primordia. PMID:12917294 cells in the presumptive midbrain neural plate require an Fgf signal to keep them from following a forebrain fate |
| GO:0030901 midbrain development | IGI PMID:23789101 Fgf22 regulated by Fgf3/Fgf8 signaling is required for zebra... | ACCEPT | Summary: fgf3/fgf8 are required for fgf22 expression and midbrain development. Reason: Miyake and Itoh: fgf3/fgf8 double morphants resemble fgf22 morphants and Fgf3/Fgf8 are needed for fgf22 expression in the posterior midbrain. Part of the MHB organizer role. Supporting Evidence: PMID:23789101 Fgf3/Fgf8 signaling was required for fgf22 expression in the posterior midbrain |
| GO:0030901 midbrain development | IMP PMID:12917294 Engrailed and Fgf8 act synergistically to maintain the bound... | ACCEPT | Summary: Fgf8 maintains midbrain identity and positions the diencephalic-mesencephalic boundary. Reason: Scholpp et al.: combined loss of Eng2/Eng3 and Fgf8 abolishes midbrain identity. Midbrain patterning is part of the MHB organizer function that defines fgf8a. Supporting Evidence: PMID:12917294 Combined loss of both Eng2/Eng3 and Fgf8 leads to complete loss of midbrain identity, resulting in fusion of the forebrain and the hindbrain primordia. PMID:12917294 cells in the presumptive midbrain neural plate require an Fgf signal to keep them from following a forebrain fate |
| GO:0030902 hindbrain development | IGI PMID:16611693 Differentiation of cerebellar cell identities in absence of ... | KEEP AS NON CORE | Summary: Fgf8 is required for proliferation and morphogenesis of the cerebellar (r1) territory. Reason: Foucher et al.: Fgf8 maintains the posterior Otx boundary and supports proliferation but is not instructive for cerebellar identities. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:16611693 Fgf8 is not instructive in establishing zebrafish cerebellar cell identities, although it is required for proliferation and morphogenesis of this territory |
| GO:0030902 hindbrain development | IMP PMID:14745965 Early requirement for fgf8 function during hindbrain pattern... | KEEP AS NON CORE | Summary: Early, nonredundant requirement for fgf8 in r5/r6 specification. Reason: Wiellette and Sive 2004 show ace mutation and fgf8 MO both suppress r5/r6 genes at early somitogenesis. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:14745965 These data demonstrate an early, nonredundant requirement for fgf8 function in hindbrain patterning. |
| GO:0030902 hindbrain development | IMP PMID:15281067 Hedgehog and Fgf signaling pathways regulate the development... | KEEP AS NON CORE | Summary: ace mutants have severely reduced hindbrain 5HT neurons. Reason: Teraoka et al. report loss of hindbrain serotonergic neurons in ace. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:15281067 Hindbrain 5HT neurons are severely reduced in mutants lacking activity of either Ace/Fgf8 or the transcription factor Noi/Pax2.1 |
| GO:0030902 hindbrain development | IMP PMID:16611693 Differentiation of cerebellar cell identities in absence of ... | KEEP AS NON CORE | Summary: Fgf8 is required for proliferation and morphogenesis of the cerebellar (r1) territory. Reason: Foucher et al.: Fgf8 maintains the posterior Otx boundary and supports proliferation but is not instructive for cerebellar identities. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:16611693 Fgf8 is not instructive in establishing zebrafish cerebellar cell identities, although it is required for proliferation and morphogenesis of this territory |
| GO:0030903 notochord development | IGI PMID:14651930 Interplay between FGF, one-eyed pinhead, and T-box transcrip... | KEEP AS NON CORE | Summary: Zoep;ace double mutants lack posterior tissues, including notochord. Reason: Genetic interaction evidence from Griffin and Kimelman. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:14651930 we show that Zoep and ace/fgf8 function are essential for the formation of all posterior tissues, including spinal cord. |
| GO:0030916 otic vesicle formation | IDA PMID:17239227 Fgf-dependent otic induction requires competence provided by... | KEEP AS NON CORE | Summary: Heat-shock fgf8 misexpression at the end of gastrulation enlarges otic vesicles. Reason: Gain-of-function evidence (recorded as IDA) from Hans et al.; it shows sufficiency within the competent field. Otic induction by fgf8a is accepted under otic placode formation. Supporting Evidence: PMID:17239227 fgf8 overexpression at the end of gastrulation, when otic induction begins, leads to much larger otic vesicles |
| GO:0030916 otic vesicle formation | IGI PMID:15188428 Genetic interactions underlying otic placode induction and f... | KEEP AS NON CORE | Summary: fgf8 interacts genetically with foxi1, fgf3 and dlx3b in otic induction. Reason: Solomon et al. report strong synergy among foxi1, fgf3 and fgf8 and weaker synergy with dlx3b. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:15188428 A strong synergistic interaction is also observed among foxi1, fgf3, and fgf8 |
| GO:0030916 otic vesicle formation | IGI PMID:15188428 Genetic interactions underlying otic placode induction and f... | KEEP AS NON CORE | Summary: fgf8 interacts genetically with foxi1, fgf3 and dlx3b in otic induction. Reason: Solomon et al. report strong synergy among foxi1, fgf3 and fgf8 and weaker synergy with dlx3b. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:15188428 A strong synergistic interaction is also observed among foxi1, fgf3, and fgf8 |
| GO:0030916 otic vesicle formation | IGI PMID:15188428 Genetic interactions underlying otic placode induction and f... | KEEP AS NON CORE | Summary: fgf8 interacts genetically with foxi1, fgf3 and dlx3b in otic induction. Reason: Solomon et al. report strong synergy among foxi1, fgf3 and fgf8 and weaker synergy with dlx3b. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:15188428 A strong synergistic interaction is also observed among foxi1, fgf3, and fgf8 |
| GO:0030916 otic vesicle formation | IMP PMID:14757644 A direct role for Fgf but not Wnt in otic placode induction. | KEEP AS NON CORE | Summary: Fgf3/Fgf8 depletion abolishes otic tissue. Reason: Phillips et al. show embryos depleted for Fgf3 and Fgf8 form no otic tissue. Supporting Evidence: PMID:14757644 Embryos that misexpress Wnt8 globally but are depleted for Fgf3 and Fgf8 produce no otic tissue. |
| GO:0030917 midbrain-hindbrain boundary development | IMP PMID:12591239 Wnt1 and wnt10b function redundantly at the zebrafish midbra... | ACCEPT | Summary: acerebellar mutants lack the MHB and isthmic organizer. Reason: The defining fgf8a phenotype: ace embryos lack the MHB constriction and the isthmic organizer; isthmic and cerebellar primordia take tectal identity; Fgf8 beads rescue. Core in vivo role of fgf8a. Supporting Evidence: PMID:9609821 Homozygous acerebellar embryos lack a cerebellum and the midbrain-hindbrain boundary organizer. PMID:9007239 The defect in ace mutant embryos is more restricted: MHB and cerebellum are absent, but a tectum is formed. PMID:14660549 cells of the isthmic and cerebellar primordia acquire a more rostral, tectal identity in the absence of the functional MHB organizer signal Fgf8 |
| GO:0030917 midbrain-hindbrain boundary development | IMP PMID:14660549 Isthmus-to-midbrain transformation in the absence of midbrai... | ACCEPT | Summary: acerebellar mutants lack the MHB and isthmic organizer. Reason: The defining fgf8a phenotype: ace embryos lack the MHB constriction and the isthmic organizer; isthmic and cerebellar primordia take tectal identity; Fgf8 beads rescue. Core in vivo role of fgf8a. Supporting Evidence: PMID:9609821 Homozygous acerebellar embryos lack a cerebellum and the midbrain-hindbrain boundary organizer. PMID:9007239 The defect in ace mutant embryos is more restricted: MHB and cerebellum are absent, but a tectum is formed. PMID:14660549 cells of the isthmic and cerebellar primordia acquire a more rostral, tectal identity in the absence of the functional MHB organizer signal Fgf8 |
| GO:0030917 midbrain-hindbrain boundary development | IMP PMID:28493069 Comparison of molecular marker expression in early zebrafish... | ACCEPT | Summary: fgf8a morphants lose epha4a at the MHB/r1 boundary. Reason: Zhang et al. (full text) used fgf8a morpholinos and saw loss of epha4a in r1 and ectopic midbrain pax6a, consistent with the ace MHB phenotype. Supporting Evidence: PMID:28493069 Epha4a expression in rhombomere R1 boundary was decreased in chronic ethanol exposure and aldh1a3 morphants, lost in fgf8a morphants |
| GO:0030917 midbrain-hindbrain boundary development | IMP PMID:9007239 Mutations in zebrafish genes affecting the formation of the ... | ACCEPT | Summary: acerebellar mutants lack the MHB and isthmic organizer. Reason: The defining fgf8a phenotype: ace embryos lack the MHB constriction and the isthmic organizer; isthmic and cerebellar primordia take tectal identity; Fgf8 beads rescue. Core in vivo role of fgf8a. Supporting Evidence: PMID:9609821 Homozygous acerebellar embryos lack a cerebellum and the midbrain-hindbrain boundary organizer. PMID:9007239 The defect in ace mutant embryos is more restricted: MHB and cerebellum are absent, but a tectum is formed. PMID:14660549 cells of the isthmic and cerebellar primordia acquire a more rostral, tectal identity in the absence of the functional MHB organizer signal Fgf8 |
| GO:0030917 midbrain-hindbrain boundary development | IMP PMID:9609821 Fgf8 is mutated in zebrafish acerebellar (ace) mutants and i... | ACCEPT | Summary: acerebellar mutants lack the MHB and isthmic organizer. Reason: The defining fgf8a phenotype: ace embryos lack the MHB constriction and the isthmic organizer; isthmic and cerebellar primordia take tectal identity; Fgf8 beads rescue. Core in vivo role of fgf8a. Supporting Evidence: PMID:9609821 Homozygous acerebellar embryos lack a cerebellum and the midbrain-hindbrain boundary organizer. PMID:9007239 The defect in ace mutant embryos is more restricted: MHB and cerebellum are absent, but a tectum is formed. PMID:14660549 cells of the isthmic and cerebellar primordia acquire a more rostral, tectal identity in the absence of the functional MHB organizer signal Fgf8 |
| GO:0031076 embryonic camera-type eye development | IMP PMID:16236770 Fgf signals from a novel signaling center determine axial pa... | KEEP AS NON CORE | Summary: Fgf8 from the telencephalon patterns the nasotemporal axis of the retina. Reason: Picker and Brand show Fgf8 induces nasal retinal fates. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:16236770 Fgf8 induces nasal and/or suppresses temporal retinal cell fates |
| GO:0035050 embryonic heart tube development | IGI PMID:16672336 Zebrafish endoderm formation is regulated by combinatorial N... | KEEP AS NON CORE | Summary: Heart tube development, genetic interaction in the endoderm/Nodal paper. Reason: The cached abstract of Poulain et al. concerns endoderm restriction by FGF/ERK and BMP; the heart tube phenotype was presumably recorded from the full text. fgf8a is required for heart development (PMID:10603341), so I defer to the curator. Supporting Evidence: PMID:10603341 These findings show that fgf8/acerebellar is required for induction and patterning of myocardial precursors. PMID:16672336 BMP and FGF-ERK pathways cooperate to restrict the number of endodermal progenitors induced in response to Nodal signalling |
| GO:0042664 negative regulation of endodermal cell fate specification | IDA PMID:16672336 Zebrafish endoderm formation is regulated by combinatorial N... | KEEP AS NON CORE | Summary: FGF/ERK signalling restricts the number of Nodal-induced endoderm progenitors. Reason: Poulain et al. show FGF/ERK and BMP cooperate to limit endoderm precursors, via phosphorylation of Casanova/Sox32. This is a gastrula-stage role of fgf8a that fgf8b, not expressed until mid-somitogenesis, cannot share. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:16672336 BMP and FGF-ERK pathways cooperate to restrict the number of endodermal progenitors induced in response to Nodal signalling |
| GO:0042664 negative regulation of endodermal cell fate specification | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Negative regulation of endodermal cell fate specification (ARBA). Reason: Consistent with the experimental rows from PMID:16672336 and PMID:17026981. Kept as non-core, like the experimental rows for the same term. Supporting Evidence: PMID:16672336 BMP and FGF-ERK pathways cooperate to restrict the number of endodermal progenitors induced in response to Nodal signalling PMID:17026981 Fgf signaling negatively regulates endoderm induction, possibly through repression of cas expression and down-regulation of Cas function |
| GO:0042664 negative regulation of endodermal cell fate specification | IGI PMID:16672336 Zebrafish endoderm formation is regulated by combinatorial N... | KEEP AS NON CORE | Summary: FGF/ERK signalling restricts the number of Nodal-induced endoderm progenitors. Reason: Poulain et al. show FGF/ERK and BMP cooperate to limit endoderm precursors, via phosphorylation of Casanova/Sox32. This is a gastrula-stage role of fgf8a that fgf8b, not expressed until mid-somitogenesis, cannot share. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:16672336 BMP and FGF-ERK pathways cooperate to restrict the number of endodermal progenitors induced in response to Nodal signalling |
| GO:0042664 negative regulation of endodermal cell fate specification | IGI PMID:16672336 Zebrafish endoderm formation is regulated by combinatorial N... | KEEP AS NON CORE | Summary: FGF/ERK signalling restricts the number of Nodal-induced endoderm progenitors. Reason: Poulain et al. show FGF/ERK and BMP cooperate to limit endoderm precursors, via phosphorylation of Casanova/Sox32. This is a gastrula-stage role of fgf8a that fgf8b, not expressed until mid-somitogenesis, cannot share. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:16672336 BMP and FGF-ERK pathways cooperate to restrict the number of endodermal progenitors induced in response to Nodal signalling |
| GO:0042664 negative regulation of endodermal cell fate specification | IGI PMID:16672336 Zebrafish endoderm formation is regulated by combinatorial N... | KEEP AS NON CORE | Summary: FGF/ERK signalling restricts the number of Nodal-induced endoderm progenitors. Reason: Poulain et al. show FGF/ERK and BMP cooperate to limit endoderm precursors, via phosphorylation of Casanova/Sox32. This is a gastrula-stage role of fgf8a that fgf8b, not expressed until mid-somitogenesis, cannot share. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:16672336 BMP and FGF-ERK pathways cooperate to restrict the number of endodermal progenitors induced in response to Nodal signalling |
| GO:0043049 otic placode formation | IGI PMID:12642489 The role of the zebrafish nodal-related genes squint and cyc... | ACCEPT | Summary: Otic placode formation, from the squint/cyclops paper. Reason: The cached abstract of Dougan et al. does not mention fgf8, but fgf8a function in otic placode induction is well established (PMID:17522161, PMID:14757644), so I defer to the curator. Supporting Evidence: PMID:17522161 fgf8 mutants depleted of RA signaling produce few otic cells, and these cells fail to form a vesicle, indicating that Fgf8 is the primary factor responsible for otic induction in RA-depleted embryos |
| GO:0043049 otic placode formation | IGI PMID:15459102 Pax8 and Pax2a function synergistically in otic specificatio... | ACCEPT | Summary: Otic placode formation (pax8/pax2a paper). Reason: Hans et al. 2004 place Pax2a and Pax8 downstream of Fgf signals in otic induction. fgf8a is one of the two inducing Fgfs, with fgf3. Supporting Evidence: PMID:15459102 competent ectodermal cells respond to Fgf signals from adjacent tissues and express two highly related paired box transcription factors Pax2a and Pax8 in the developing placode PMID:17522161 fgf8 mutants depleted of RA signaling produce few otic cells, and these cells fail to form a vesicle, indicating that Fgf8 is the primary factor responsible for otic induction in RA-depleted embryos |
| GO:0043049 otic placode formation | IMP PMID:15459102 Pax8 and Pax2a function synergistically in otic specificatio... | ACCEPT | Summary: Otic placode formation (pax8/pax2a paper). Reason: Hans et al. 2004 place Pax2a and Pax8 downstream of Fgf signals in otic induction. fgf8a is one of the two inducing Fgfs, with fgf3. Supporting Evidence: PMID:15459102 competent ectodermal cells respond to Fgf signals from adjacent tissues and express two highly related paired box transcription factors Pax2a and Pax8 in the developing placode PMID:17522161 fgf8 mutants depleted of RA signaling produce few otic cells, and these cells fail to form a vesicle, indicating that Fgf8 is the primary factor responsible for otic induction in RA-depleted embryos |
| GO:0043049 otic placode formation | IMP PMID:17522161 Changes in retinoic acid signaling alter otic patterning. | ACCEPT | Summary: fgf8 mutants depleted of RA form few otic cells and no vesicle. Reason: Hans and Westerfield identify Fgf8 as the primary otic inducer in RA-depleted embryos. Supporting Evidence: PMID:17522161 fgf8 mutants depleted of RA signaling produce few otic cells, and these cells fail to form a vesicle, indicating that Fgf8 is the primary factor responsible for otic induction in RA-depleted embryos |
| GO:0043049 otic placode formation | IMP PMID:17522161 Changes in retinoic acid signaling alter otic patterning. | ACCEPT | Summary: fgf8 mutants depleted of RA form few otic cells and no vesicle. Reason: Hans and Westerfield identify Fgf8 as the primary otic inducer in RA-depleted embryos. Supporting Evidence: PMID:17522161 fgf8 mutants depleted of RA signaling produce few otic cells, and these cells fail to form a vesicle, indicating that Fgf8 is the primary factor responsible for otic induction in RA-depleted embryos |
| GO:0043049 otic placode formation | IMP PMID:24677486 Mesodermal Fgf10b cooperates with other fibroblast growth fa... | ACCEPT | Summary: Otic induction in fgf8 x15 mutants with fgf10b knockdown. Reason: Maulding et al. (full text) use the fgf8 x15 mutant; otic induction by Fgf3 and Fgf8 is conserved across species. Supporting Evidence: PMID:24677486 the process of otic induction in highly conserved, with important roles for Fgf3 and Fgf8 reported in all species examined |
| GO:0043410 positive regulation of MAPK cascade | IBA GO_REF:0000033 | ACCEPT | Summary: Positive regulation of MAPK cascade (IBA). Reason: FGF ligands activate Ras/MAPK; Sef was identified as a feedback antagonist of Fgf8-induced Ras/MAPK signalling (PMID:11802165). Supporting Evidence: PMID:11802165 FGFs regulate dorsoventral patterning by controlling ventral bone morphogenetic protein (BMP) expression. |
| GO:0046850 regulation of bone remodeling | IEP PMID:17448458 Fgf8 haploinsufficiency results in distinct craniofacial def... | MARK AS OVER ANNOTATED | Summary: Regulation of bone remodeling, from fgf8 expression in the adult craniofacial skeleton (IEP). Reason: Expression of fgf8 in adult craniofacial bone is consistent with a role there but cannot by itself show regulation of bone remodeling. The functional claim rests on the IMP from the same paper, which is kept. Supporting Evidence: PMID:17448458 skeletal defects observed in ace(ti282a)/fgf8 heterozygotes are consistent with expression patterns of fgf8 in the mature craniofacial skeleton |
| GO:0046850 regulation of bone remodeling | IMP PMID:17448458 Fgf8 haploinsufficiency results in distinct craniofacial def... | KEEP AS NON CORE | Summary: ace/fgf8 heterozygous adults show craniofacial skeletal defects and increased bone metabolism. Reason: Albertson and Yelick (full text) describe haploinsufficient adult skeletal phenotypes. The ace ti282a allele carries a premature stop codon. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:17448458 may be related to increased levels of bone metabolism observed in ace(ti282a)/fgf8 heterozygotes |
| GO:0048263 determination of dorsal identity | IDA PMID:16961592 Genomic organization, alternative splicing, and multiple reg... | KEEP AS NON CORE | Summary: fgf8 mRNA injection dorsalises embryos (both splice isoforms). Reason: Inoue et al. show both Fgf8 splice variants dorsalise the embryo. Gain-of-function data consistent with the D/V role. Note: "Fgf8a/Fgf8b" in this paper are splice isoforms of fgf8a, not the paralogues. Supporting Evidence: PMID:16961592 both variants have dorsalizing activities on zebrafish embryos, with Fgf8b being more potent |
| GO:0048339 paraxial mesoderm development | IGI PMID:14651930 Interplay between FGF, one-eyed pinhead, and T-box transcrip... | KEEP AS NON CORE | Summary: Paraxial mesoderm development, Zoep;ace interaction. Reason: Genetic interaction from Griffin and Kimelman. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:14651930 we show that Zoep and ace/fgf8 function are essential for the formation of all posterior tissues, including spinal cord. |
| GO:0048339 paraxial mesoderm development | IGI PMID:32345657 Fgf-driven Tbx protein activities directly induce myf5 and m... | KEEP AS NON CORE | Summary: Fgf signalling acts through Tbx16/Tbxta to initiate trunk myogenesis in paraxial mesoderm. Reason: Osborn et al. (full text) show dorsally derived Fgf signals act through Tbx16 and Tbxta to induce muscle precursors. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:32345657 dorsally derived Fgf signals act through Tbx16 and Tbxta to induce slow and fast trunk muscle precursors at distinct dorsoventral positions |
| GO:0048339 paraxial mesoderm development | IGI PMID:32345657 Fgf-driven Tbx protein activities directly induce myf5 and m... | KEEP AS NON CORE | Summary: Fgf signalling acts through Tbx16/Tbxta to initiate trunk myogenesis in paraxial mesoderm. Reason: Osborn et al. (full text) show dorsally derived Fgf signals act through Tbx16 and Tbxta to induce muscle precursors. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:32345657 dorsally derived Fgf signals act through Tbx16 and Tbxta to induce slow and fast trunk muscle precursors at distinct dorsoventral positions |
| GO:0048665 neuron fate specification | IGI PMID:16256099 Fgf19 regulated by Hh signaling is required for zebrafish fo... | UNDECIDED | Summary: Neuron fate specification, fgf3/fgf8 knockdown in the Fgf19 paper. Reason: The cached abstract of Miyake et al. concerns Fgf19 and mentions Fgf3/Fgf8 only as upstream brain-patterning signals that do not control fgf19 expression. I cannot see the fgf3/fgf8 double-knockdown result on which this annotation rests. Supporting Evidence: PMID:16256099 Fgf3 and Fgf8 are crucial for the formation of the forebrain and hindbrain. |
| GO:0048702 embryonic neurocranium morphogenesis | IGI PMID:27060628 An Fgf-Shh signaling hierarchy regulates early specification... | KEEP AS NON CORE | Summary: Fgf signalling specifies mesodermal progenitors of the postchordal neurocranium. Reason: McCarthy et al. show early Fgf signalling is needed for has2 expression in cephalic mesoderm and postchordal neurocranium development. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:27060628 Fibroblast growth factor (Fgf) signaling for early specification of mesodermally-derived progenitor cells |
| GO:0048705 skeletal system morphogenesis | IMP PMID:17448458 Fgf8 haploinsufficiency results in distinct craniofacial def... | KEEP AS NON CORE | Summary: Craniofacial skeletal defects in adult ace heterozygotes. Reason: Adult haploinsufficiency phenotype. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:17448458 may be related to increased levels of bone metabolism observed in ace(ti282a)/fgf8 heterozygotes |
| GO:0048709 oligodendrocyte differentiation | IGI PMID:16256099 Fgf19 regulated by Hh signaling is required for zebrafish fo... | UNDECIDED | Summary: Oligodendrocyte differentiation, fgf3/fgf8 knockdown in the Fgf19 paper. Reason: As for neuron fate specification from the same paper: the cached abstract does not show the fgf3/fgf8 result. Supporting Evidence: PMID:16256099 Fgf3 and Fgf8 are crucial for the formation of the forebrain and hindbrain. |
| GO:0048839 inner ear development | IMP PMID:16754885 Mutation of the atrophin2 gene in the zebrafish disrupts sig... | KEEP AS NON CORE | Summary: fgf8 loss gives fused otoliths and abnormal semicircular canals. Reason: Asai et al. describe the inner-ear phenotype of fgf8 loss, which the atrophin2 mutant resembles. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:16754885 whose phenotypic characteristics resembled those of null mutants for the gene encoding fibroblast growth factor 8 (Fgf8): an inconsistent startle response, circular swimming, fused otoliths, and abnormal semicircular canals |
| GO:0048839 inner ear development | IMP PMID:9007239 Mutations in zebrafish genes affecting the formation of the ... | KEEP AS NON CORE | Summary: Inner ear development, from the original ace screen paper. Reason: The cached abstract of Brand et al. 1996 focuses on MHB; ear defects of fgf8 loss are documented elsewhere (PMID:16754885). Deferring to the curator. Supporting Evidence: PMID:16754885 whose phenotypic characteristics resembled those of null mutants for the gene encoding fibroblast growth factor 8 (Fgf8): an inconsistent startle response, circular swimming, fused otoliths, and abnormal semicircular canals |
| GO:0051146 striated muscle cell differentiation | IMP PMID:16120642 Fgf8 drives myogenic progression of a novel lateral fast mus... | KEEP AS NON CORE | Summary: Fgf8 is required for differentiation of lateral fast muscle fibres. Reason: Groves et al. (ace mutants and morphants). Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:16120642 we show that Fgf8 signalling in the somite is required for myod expression and terminal differentiation of a subset of fast muscle cells in the zebrafish lateral somite |
| GO:0051146 striated muscle cell differentiation | IMP PMID:16120642 Fgf8 drives myogenic progression of a novel lateral fast mus... | KEEP AS NON CORE | Summary: Fgf8 is required for differentiation of lateral fast muscle fibres. Reason: Groves et al. (ace mutants and morphants). Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:16120642 we show that Fgf8 signalling in the somite is required for myod expression and terminal differentiation of a subset of fast muscle cells in the zebrafish lateral somite |
| GO:0051216 cartilage development | IMP PMID:14651935 Fgf signalling is required for formation of cartilage in the... | KEEP AS NON CORE | Summary: fgf8 knockdown has mild cartilage effects, severe when combined with fgf3. Reason: Walshe and Mason: Fgf8 inhibition alone has variable, mild effects on head cartilage; with Fgf3 inhibition all pharyngeal cartilage is lost. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:14651935 Inhibition of Fgf8 alone has variable, but mild, effects. However, inhibition of both Fgf3 and Fgf8 together causes a complete absence of pharyngeal cartilages and the near-complete loss of the neurocranial cartilage. |
| GO:0051216 cartilage development | IMP PMID:15509770 An essential role for Fgfs in endodermal pouch formation inf... | KEEP AS NON CORE | Summary: Fgf8/Fgf3 reduction causes hyoid and branchial cartilage loss. Reason: Crump et al. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:15509770 animals doubly reduced for Fgf8 and Fgf3 have severe reductions in hyoid cartilages and the more posterior branchial cartilages |
| GO:0051216 cartilage development | IMP PMID:16754885 Mutation of the atrophin2 gene in the zebrafish disrupts sig... | KEEP AS NON CORE | Summary: Cartilage development (atrophin2 paper). Reason: Asai et al. (full text) include fgf8 morphants as a comparison for the atrophin2 phenotype. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:16754885 whose phenotypic characteristics resembled those of null mutants for the gene encoding fibroblast growth factor 8 (Fgf8): an inconsistent startle response, circular swimming, fused otoliths, and abnormal semicircular canals |
| GO:0055011 atrial cardiac muscle cell differentiation | IMP NOT PMID:19395641 Distinct phases of cardiomyocyte differentiation regulate gr... | ACCEPT | Summary: NOT: fgf8 is not required for atrial (venous pole) cardiomyocyte addition. Reason: De Pater et al. show fgf8 morphants lose late-differentiating cardiomyocytes at the arterial pole but not at the venous pole. The negated annotation is supported. Supporting Evidence: PMID:19395641 Our data demonstrate that cardiomyocyte differentiation at the arterial pole is independent of Isl1 but requires Fgf8 signaling. PMID:19395641 while the number of eGFP pos DsRed neg cells at the venous pole did not change significantly |
| GO:0055012 ventricular cardiac muscle cell differentiation | IMP PMID:19395641 Distinct phases of cardiomyocyte differentiation regulate gr... | KEEP AS NON CORE | Summary: Late cardiomyocyte addition at the arterial pole requires Fgf8. Reason: De Pater et al. (full text). Refines the accepted cardiac progenitor role. Supporting Evidence: PMID:19395641 Our data demonstrate that cardiomyocyte differentiation at the arterial pole is independent of Isl1 but requires Fgf8 signaling. |
| GO:0060037 pharyngeal system development | IGI PMID:17576618 REREa/Atrophin-2 interacts with histone deacetylase and Fgf8... | KEEP AS NON CORE | Summary: rerea interacts genetically with fgf8 in pharyngeal development. Reason: Plaster et al.: loss of REREa or HDAC synergises with loss of Fgf8 in pharyngeal cartilage and other tissues. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:17576618 removing the functions of either REREa or HDAC synergizes with loss of Fgf8 function to disrupt posterior mesoderm formation during somitogenesis, midbrain-hindbrain boundary maintenance, and pharyngeal cartilage development |
| GO:0060037 pharyngeal system development | IGI PMID:25142463 Tbx1 controls the morphogenesis of pharyngeal pouch epitheli... | KEEP AS NON CORE | Summary: Mesodermal Fgf8a guides pharyngeal pouch morphogenesis downstream of Tbx1. Reason: Choe and Crump (full text): compound loss of wnt11r and fgf8a phenocopies tbx1 pouch defects, and Fgf8a is a guidance cue for migrating pouch cells. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:25142463 compound losses of wnt11r and fgf8a phenocopy tbx1 mutant pouch defects PMID:25142463 Fgf8a acts as a Wnt11r-dependent guidance cue for migrating pouch cells |
| GO:0060041 retina development in camera-type eye | IGI PMID:15809038 Differentiation of the vertebrate retina is coordinated by a... | KEEP AS NON CORE | Summary: Fgf8 and Fgf3 coordinate the onset of retinal differentiation. Reason: Martinez-Morales et al. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:15809038 The concerted activity of Fgf8 and Fgf3 is both necessary and sufficient to coordinate retinal differentiation independent of the connecting optic stalk. |
| GO:0060059 embryonic retina morphogenesis in camera-type eye | IGI PMID:19823566 Dynamic coupling of pattern formation and morphogenesis in t... | KEEP AS NON CORE | Summary: Fgf8/3/24 control nasal retina identity and eye morphogenesis. Reason: Picker et al. 2009 (full text), triple mutant/morphant analysis. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:19823566 Triple-mutant analysis shows that this combined Fgf signal fully controls nasal retina identity by regulating the nasal transcription factor Foxg1. |
| GO:0060271 cilium assembly | IGI PMID:23946439 Differential roles for 3-OSTs in the regulation of cilia len... | KEEP AS NON CORE | Summary: ace interacts with 3-OST-5 in Kupffer's vesicle cilia length. Reason: Neugebauer et al. (full text) place 3-OST-5 in the FGF pathway controlling KV cilia length. Cilium assembly is a downstream readout of Fgf8 signalling via ier2/fibp1 and foxj1a; fgf8a is not part of the ciliogenesis machinery. Supporting Evidence: PMID:23946439 3-OST-5 functions in the fibroblast growth factor pathway to control cilia length via the ciliogenic transcription factors FoxJ1a and Rfx2. PMID:19164561 Cilia are also lost after suppression of FGF8, but can be rescued by injection of ier2 and fibp1 mRNA. |
| GO:0060271 cilium assembly | IMP PMID:19164561 FGF-dependent left-right asymmetry patterning in zebrafish i... | KEEP AS NON CORE | Summary: Kupffer's vesicle cilia are lost after fgf8 knockdown. Reason: Hong and Dawid (full text): loss of KV cilia after Fgf8 suppression, rescued by ier2 and fibp1. Upstream signalling role, not part of the assembly machinery. Supporting Evidence: PMID:19164561 Cilia are also lost after suppression of FGF8, but can be rescued by injection of ier2 and fibp1 mRNA. |
| GO:0060788 ectodermal placode formation | IMP PMID:20885782 Identification of early requirements for preplacodal ectoder... | KEEP AS NON CORE | Summary: Fgf8 misexpression can induce preplacodal ectoderm. Reason: Kwon et al. (full text). Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:20885782 Localized ventral misexpression of Fgf8 and Chordin can activate ectopic preplacodal development anywhere within the zone of competence |
| GO:0061053 somite development | IMP PMID:9609821 Fgf8 is mutated in zebrafish acerebellar (ace) mutants and i... | KEEP AS NON CORE | Summary: Somite development in ace mutants. Reason: Reifers et al. 1998 describe fgf8 expression and requirements during somitogenesis. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:9609821 we show that acerebellar is a zebrafish Fgf8 mutation that may inactivate Fgf8 function |
| GO:0061195 taste bud formation | IMP PMID:21791527 Fgf signaling controls pharyngeal taste bud formation throug... | KEEP AS NON CORE | Summary: ace mutants have reduced taste buds. Reason: Kapsimali et al. show compromised Fgf signalling reduces taste buds. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:21791527 compromised Fgf signaling in the larva results in taste bud reduction and disorganization |
| GO:0061386 closure of optic fissure | IGI PMID:29625437 Metalloproteinase Adamts16 Is Required for Proper Closure of... | KEEP AS NON CORE | Summary: Optic fissure closure: fgf8 is upregulated in adamts16 morphants (genetic interaction). Reason: Cao et al. show adamts16 restricts fgf8 in the optic cup; the IGI presumably records rescue by fgf8 knockdown. fgf8a here acts as a signal whose excess impairs closure. Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:29625437 fibroblast growth factor 8 (fgf8) was ectopically upregulated in the OC |
| GO:0070121 Kupffer's vesicle development | IMP PMID:19164561 FGF-dependent left-right asymmetry patterning in zebrafish i... | ACCEPT | Summary: Kupffer's vesicle development requires Fgf8. Reason: Hong and Dawid and Albertson and Yelick show that KV and its cilia depend on fgf8; this underlies the left-right role. Supporting Evidence: PMID:19164561 Cilia are also lost after suppression of FGF8, but can be rescued by injection of ier2 and fibp1 mRNA. PMID:15932752 Approximately 1/3 of zebrafish ace/fgf8 mutants are missing Kupffer's vesicle (KV) |
| GO:0071599 otic vesicle development | IGI PMID:24677486 Mesodermal Fgf10b cooperates with other fibroblast growth fa... | KEEP AS NON CORE | Summary: Otic vesicle development in fgf8 mutants with fgf10b/fgf3 knockdown. Reason: Maulding et al. (full text). Developmental phenotype readout of fgf8a loss (ace mutant, morpholino, or combined knockdown with another Fgf or pathway gene). fgf8a is a secreted FGFR ligand, so this is an acts_upstream_of_or_within role of the signal in a tissue that responds to it, not a core molecular activity. Supporting Evidence: PMID:24677486 the process of otic induction in highly conserved, with important roles for Fgf3 and Fgf8 reported in all species examined |
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Download this section (compressed HTML)Q: Does fgf8b expression rise in ace (ti282a, premature stop codon) mutants, as transcriptional adaptation would predict, and does it buffer shared domains such as the MHB and somites?
Q: Would fgf8b coding sequence expressed from the fgf8a locus rescue ace, confirming that the two proteins are interchangeable in vivo?
Q: What is the expression pattern of the single fgf8 gene of spotted gar, and does it include the heart, gastrula margin and telencephalon (fgf8a-only domains in zebrafish)?
Experiment: Knock-in of fgf8b coding sequence into the fgf8a locus (or fgf8b mRNA injection into ace mutants) and scoring of MHB, heart and Kupffer's vesicle phenotypes.
Hypothesis: fgf8a and fgf8b proteins are functionally equivalent; their differences are regulatory.
Type: cross-rescue
Experiment: Compare ace single mutants with fgf8a;fgf8b double mutants, using a promoter-deletion (RNA-less) fgf8a allele to avoid transcriptional adaptation.
Hypothesis: fgf8a and fgf8b act redundantly in their shared domains (MHB, somites, otic vesicle).
Type: double mutant analysis
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Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)