fgf8b is one of two zebrafish co-orthologues of vertebrate FGF8 retained from the teleost-specific genome duplication (the other is fgf8a). It was first described as zebrafish fgf17 (fgf17a). It encodes a secreted fibroblast growth factor of the FGF8/17/18 (FgfD) subfamily, with an N-terminal signal peptide and the FGF core domain, about 71% identical to fgf8a, and acts like fgf8a when misexpressed. Unlike fgf8a it is not expressed during gastrulation. It is first expressed at mid-somitogenesis in the ventral midbrain-hindbrain boundary and anterior somites, then in the optic stalks, otic vesicle, hyoid region and dorsal diencephalon. Its midbrain-hindbrain boundary expression depends on pax2a and is maintained by fgf8a. It is absent from the heart and from the fin bud, telencephalon and pharyngeal arches, where fgf8a is expressed. Its in vivo function has not been tested by loss of function; it is thought to act with fgf8a as an organizer signal at the midbrain-hindbrain boundary.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005104 fibroblast growth factor receptor binding | NAS PMID:11091072 Overlapping and distinct functions provided by fgf17, a new ... | ACCEPT | Summary: Binds FGF receptors (author statement, first description of zebrafish fgf17 = fgf8b). Reason: fgf8b is a TGD co-orthologue of FGF8 with the FGF core domain, a signal peptide and 70.8% identity to fgf8a; injected fgf8b (then called fgf17) acts like fgf8. The ligand activity is therefore retained at the protein level and shared with fgf8a. The NAS is consistent with the more specific IBA FGFR1/FGFR2 binding rows. Supporting Evidence: PMID:11091072 Fgf8 and Fgf17 act as hierarchically organized signaling molecules during development of the MHB organizer and possibly other organizers in the developing nervous system PMID:11091072 fgf17 can act similar to fgf8 during gastrulation, when fgf17 is not normally expressed |
| GO:0005105 type 1 fibroblast growth factor receptor binding | IBA GO_REF:0000033 | ACCEPT | Summary: Binding to type 1 FGF receptor (IBA, FGF8/17/18 node PTN007510376). Reason: fgf8b lies inside the FgfD clade covered by the PAINT node, and there is no evidence of protein-level divergence. fgf8b is a TGD co-orthologue of FGF8 with the FGF core domain, a signal peptide and 70.8% identity to fgf8a; injected fgf8b (then called fgf17) acts like fgf8. The ligand activity is therefore retained at the protein level and shared with fgf8a. Supporting Evidence: PMID:17708537 the teleost genes called fgf8 and fgf17a are duplicates of the tetrapod gene Fgf8, and thus should be called fgf8a and fgf8b PMID:11091072 fgf17 can act similar to fgf8 during gastrulation, when fgf17 is not normally expressed |
| GO:0005111 type 2 fibroblast growth factor receptor binding | IBA GO_REF:0000033 | ACCEPT | Summary: Binding to type 2 FGF receptor (IBA, FGF8/17/18 node PTN007510376). Reason: fgf8b lies inside the FgfD clade covered by the PAINT node, and there is no evidence of protein-level divergence. fgf8b is a TGD co-orthologue of FGF8 with the FGF core domain, a signal peptide and 70.8% identity to fgf8a; injected fgf8b (then called fgf17) acts like fgf8. The ligand activity is therefore retained at the protein level and shared with fgf8a. Supporting Evidence: PMID:17708537 the teleost genes called fgf8 and fgf17a are duplicates of the tetrapod gene Fgf8, and thus should be called fgf8a and fgf8b PMID:11091072 fgf17 can act similar to fgf8 during gastrulation, when fgf17 is not normally expressed |
| GO:0005576 extracellular region | IBA GO_REF:0000033 | ACCEPT | Summary: Active in the extracellular region (secreted ligand, IBA). Reason: fgf8b has an N-terminal signal peptide, like fgf8a, whose extracellular spreading is directly shown (PMID:15498491). Supporting Evidence: file:DANRE/fgf8b/fgf8b-uniprot.txt SIGNAL 1..27 file:DANRE/fgf8b/fgf8b-uniprot.txt SUBCELLULAR LOCATION: Secreted |
| GO:0005576 extracellular region | IEA GO_REF:0000044 | ACCEPT | Summary: Secreted (UniProt subcellular location mapping). Reason: Consistent with the signal peptide. Supporting Evidence: file:DANRE/fgf8b/fgf8b-uniprot.txt SUBCELLULAR LOCATION: Secreted file:DANRE/fgf8b/fgf8b-uniprot.txt SIGNAL 1..27 |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Cytoplasm, propagated from the FGF family root node. Reason: As for fgf8a and human FGF8: the node PTN000160075 covers intracellular FGFs as well as secreted ones, and fgf8b has a signal peptide and is a secreted ligand. 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 including intracellular and non-classically secreted FGFs; fgf8b has a signal peptide. Supporting Evidence: file:DANRE/fgf8b/fgf8b-uniprot.txt SIGNAL 1..27 |
| GO:0007389 pattern specification process | NAS PMID:11091072 Overlapping and distinct functions provided by fgf17, a new ... | KEEP AS NON CORE | Summary: Pattern specification process (author statement). Reason: Reifers et al. propose that Fgf8 and Fgf17 (= fgf8b) act hierarchically in the MHB organizer and possibly other neural organizers. The statement rests on expression and gain of function, not on loss of fgf8b function, which has not been published. Broad and non-core. Supporting Evidence: PMID:11091072 Fgf8 and Fgf17 act as hierarchically organized signaling molecules during development of the MHB organizer and possibly other organizers in the developing nervous system |
| GO:0007498 mesoderm development | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Mesoderm development (ARBA machine-learning inference). Reason: The fgf8a evidence behind this kind of rule is gastrula-stage mesoderm formation (ace;oep interactions). fgf8b is not expressed during gastrulation and has no loss-of-function data; its somite expression begins at the 8-somite stage. The inference is not supported for fgf8b. Its paralogue fgf8a keeps this term. Supporting Evidence: file:DANRE/fgf8b/fgf8b-uniprot.txt Not expressed during gastrulation. |
| GO:0008083 growth factor activity | IBA GO_REF:0000033 | ACCEPT | Summary: Growth factor activity (IBA). Reason: fgf8b is a TGD co-orthologue of FGF8 with the FGF core domain, a signal peptide and 70.8% identity to fgf8a; injected fgf8b (then called fgf17) acts like fgf8. The ligand activity is therefore retained at the protein level and shared with fgf8a. Supporting Evidence: PMID:11091072 fgf17 can act similar to fgf8 during gastrulation, when fgf17 is not normally expressed |
| GO:0008083 growth factor activity | IEA GO_REF:0000002 | ACCEPT | Summary: Growth factor activity (InterPro FGF family mapping). Reason: fgf8b is a TGD co-orthologue of FGF8 with the FGF core domain, a signal peptide and 70.8% identity to fgf8a; injected fgf8b (then called fgf17) acts like fgf8. The ligand activity is therefore retained at the protein level and shared with fgf8a. Supporting Evidence: PMID:11091072 fgf17 can act similar to fgf8 during gastrulation, when fgf17 is not normally expressed |
| GO:0008284 positive regulation of cell population proliferation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Positive regulation of cell population proliferation (IBA). Reason: Generic FGF mitogenic role; no fgf8b-specific data. Kept as non-core, as for fgf8a and human FGF8. Supporting Evidence: PMID:11091072 fgf17 can act similar to fgf8 during gastrulation, when fgf17 is not normally expressed |
| GO:0008543 fibroblast growth factor receptor signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: FGF receptor signaling pathway (IBA). Reason: Core pathway for an FGF ligand; protein-level activity is retained (injection assay). Supporting Evidence: PMID:11091072 fgf17 can act similar to fgf8 during gastrulation, when fgf17 is not normally expressed |
| GO:0008543 fibroblast growth factor receptor signaling pathway | NAS PMID:11091072 Overlapping and distinct functions provided by fgf17, a new ... | ACCEPT | Summary: FGF receptor signaling pathway (author statement). Reason: Consistent with the IBA. Supporting Evidence: PMID:11091072 Fgf8 and Fgf17 act as hierarchically organized signaling molecules during development of the MHB organizer and possibly other organizers in the developing nervous system |
| GO:0009952 anterior/posterior pattern specification | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Anterior/posterior pattern specification (ARBA). Reason: No fgf8b-specific evidence. The fgf8a data for this term are from gastrula and early neural plate patterning, before fgf8b is expressed. Supporting Evidence: file:DANRE/fgf8b/fgf8b-uniprot.txt Not expressed during gastrulation. |
| GO:0009953 dorsal/ventral pattern formation | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Dorsal/ventral pattern formation (IBA, FgfD node PTN002608342). Reason: The PAINT node is sound: zebrafish fgf8a, fgf24 and mouse Fgf8 act in D/V patterning, and fgf8b protein can act like fgf8 when injected during gastrulation. But the embryonic D/V axis is set in the blastula and gastrula, when fgf8b is not expressed; the in vivo role is carried by fgf8a (PMID:15151985). This is an expression-level loss of an ancestral subfunction in one copy, which IBA propagation cannot see. fgf8a keeps the term. Propagation Review Root cause: PROPAGATION BAD Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: PANTHER:PTN002608342 SUPPORTS SOURCE BUT NOT TARGET Node is supported by fgf8a, fgf24 and mouse Fgf8; fgf8b retains protein activity but is not expressed at the stages when the D/V axis is patterned. Supporting Evidence: file:DANRE/fgf8b/fgf8b-uniprot.txt Not expressed during gastrulation. PMID:11091072 fgf17 can act similar to fgf8 during gastrulation, when fgf17 is not normally expressed PMID:15151985 we show that loss of Fgf8 function enhances the ventralisation of chordin-deficient embryos |
| GO:0022008 neurogenesis | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Neurogenesis (IBA). Reason: Plausible from expression at the MHB and in the dorsal diencephalon, but broad and without fgf8b-specific data. Non-core. Supporting Evidence: PMID:19562753 with strong expression of both genes in both species in the midbrain-hindbrain border (MBH) and somites (Fig. 6A–H) |
| GO:0030334 regulation of cell migration | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Regulation of cell migration (IBA). Reason: Generic FGF-family role; no fgf8b-specific data. Non-core. Supporting Evidence: PMID:11091072 fgf17 can act similar to fgf8 during gastrulation, when fgf17 is not normally expressed |
| GO:0030917 midbrain-hindbrain boundary development | NAS PMID:11091072 Overlapping and distinct functions provided by fgf17, a new ... | KEEP AS NON CORE | Summary: Midbrain-hindbrain boundary development (author statement). Reason: fgf8b is expressed in the MHB, where its maintenance depends on fgf8a and its expression on pax2a dose; the authors propose a hierarchical role with fgf8a. No loss-of-function test exists, and the only double-loss experiment (ace;noi, lacking both) was scored for dopaminergic neurons only (PMID:12843251). Kept as non-core: plausible and consistent with the shared MHB domain, but not demonstrated. Supporting Evidence: PMID:11091072 only maintenance of fgf17 expression is disturbed at the MHB of acerebellar/fgf8 mutants PMID:11091072 Analysis of zebrafish MHB mutants demonstrates a gene-dosage dependent requirement of fgf17 expression for the no isthmus// pax2.1 gene PMID:19562753 with strong expression of both genes in both species in the midbrain-hindbrain border (MBH) and somites (Fig. 6A–H) |
| GO:0042664 negative regulation of endodermal cell fate specification | IEA GO_REF:0000117 | REMOVE | Summary: Negative regulation of endodermal cell fate specification (ARBA). Reason: This is a blastula/gastrula process: FGF/ERK signalling limits Nodal-induced endoderm progenitors (PMID:16672336), a role of fgf8a. fgf8b is not expressed during gastrulation and there is no evidence that it acts in endoderm specification. The machine inference should not be carried to fgf8b. Supporting Evidence: file:DANRE/fgf8b/fgf8b-uniprot.txt Not expressed during gastrulation. PMID:16672336 BMP and FGF-ERK pathways cooperate to restrict the number of endodermal progenitors induced in response to Nodal signalling |
| GO:0043410 positive regulation of MAPK cascade | IBA GO_REF:0000033 | ACCEPT | Summary: Positive regulation of MAPK cascade (IBA). Reason: Canonical output of FGF ligand signalling; protein activity is retained. Supporting Evidence: PMID:11091072 fgf17 can act similar to fgf8 during gastrulation, when fgf17 is not normally expressed |
Loading supporting content…
Download this section (compressed HTML)Q: Does fgf8b have any in vivo function on its own? No fgf8b mutant or morphant phenotype has been published.
Q: Is fgf8b upregulated in ace (premature-stop) mutants, and does it contribute to the residual MHB and somite signalling there?
Experiment: Generate fgf8b null alleles (including a promoter-deletion, RNA-less allele) and analyse single mutants and fgf8a;fgf8b double mutants for MHB, cerebellum, somite muscle and otic phenotypes.
Hypothesis: fgf8b is dispensable alone but acts redundantly with fgf8a at the MHB and in somites.
Type: double mutant analysis
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)