pax6b is one of two zebrafish co-orthologues of vertebrate PAX6, retained from the teleost-specific genome duplication. It encodes a transcription factor with a paired domain and a paired-type homeodomain that binds cis-regulatory DNA and activates target genes with the same efficiency as its paralogue pax6a. pax6b is expressed in the developing retina and lens placode, in restricted domains of the dorsal diencephalon, midbrain-hindbrain boundary and hindbrain, and, uniquely among the two copies, in pancreatic and intestinal endocrine cells. It is required for lens and anterior eye segment (cornea, iris) development, a role that depends on its homeodomain, and for the differentiation of pancreatic endocrine cells, where it promotes beta and delta cell fates and restrains ghrelin-expressing epsilon cells, a role that does not require the homeodomain. It similarly balances enteroendocrine cell subtypes in the intestine, and it initiates proliferation of Muller glia-derived neuronal progenitors during adult retinal regeneration. The homozygous-viable sunrise mutant carries a pax6b homeodomain missense allele (L244P).
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: Sequence-specific binding of RNA polymerase II cis-regulatory DNA via the paired domain and homeodomain. Reason: Both zebrafish Pax6 co-orthologues retain complete paired domains and homeodomains and activate paired-domain (CD19) and homeodomain (P3) reporter targets at indistinguishable levels in the same assay (PMID:18282108); both act as transcriptional activators and both induce ectopic eyes in Drosophila (PMID:9831649). The molecular function is therefore conserved in both copies and is correctly shared across the pair. The sunrise L244P mutation reduces binding to the P2/P3 homeodomain target sites in EMSA (PMID:18282108). Supporting Evidence: PMID:18282108 Activation by the two wild type co-orthologues through the P3 homeodomain target [45] (Figure 1D), or the CD19 paired domain target [46] (Figure 1E), was not significantly different, in contrast to the original observations by Nornes et al [43]. PMID:18282108 Sequencing of sri homozygotes and heterozygotes identified a leucine to proline missense mutation in a highly conserved residue of the pax6b homeodomain (Figures 1B, S1B, and S1C). |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IBA GO_REF:0000033 | ACCEPT | Summary: pax6b encodes a paired/homeodomain DNA-binding transcription factor with directly measured transactivation activity. Reason: Both zebrafish Pax6 co-orthologues retain complete paired domains and homeodomains and activate paired-domain (CD19) and homeodomain (P3) reporter targets at indistinguishable levels in the same assay (PMID:18282108); both act as transcriptional activators and both induce ectopic eyes in Drosophila (PMID:9831649). The molecular function is therefore conserved in both copies and is correctly shared across the pair. The sunrise L244P homeodomain mutation reduces DNA binding and abolishes P3 activation, confirming that the activity depends on the DNA-binding domains. Supporting Evidence: PMID:18282108 Activation by the two wild type co-orthologues through the P3 homeodomain target [45] (Figure 1D), or the CD19 paired domain target [46] (Figure 1E), was not significantly different, in contrast to the original observations by Nornes et al [43]. PMID:9831649 Both Pax6.1 and Pax6.2 can act as transcriptional activators with Pax6.2 being more efficient than Pax6.1. PMID:18282108 Sequencing of sri homozygotes and heterozygotes identified a leucine to proline missense mutation in a highly conserved residue of the pax6b homeodomain (Figures 1B, S1B, and S1C). |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IDA PMID:18282108 Subfunctionalization of duplicated zebrafish pax6 genes by c... | ACCEPT | Summary: pax6b encodes a paired/homeodomain DNA-binding transcription factor with directly measured transactivation activity. Reason: Both zebrafish Pax6 co-orthologues retain complete paired domains and homeodomains and activate paired-domain (CD19) and homeodomain (P3) reporter targets at indistinguishable levels in the same assay (PMID:18282108); both act as transcriptional activators and both induce ectopic eyes in Drosophila (PMID:9831649). The molecular function is therefore conserved in both copies and is correctly shared across the pair. The sunrise L244P homeodomain mutation reduces DNA binding and abolishes P3 activation, confirming that the activity depends on the DNA-binding domains. Supporting Evidence: PMID:18282108 Activation by the two wild type co-orthologues through the P3 homeodomain target [45] (Figure 1D), or the CD19 paired domain target [46] (Figure 1E), was not significantly different, in contrast to the original observations by Nornes et al [43]. PMID:9831649 Both Pax6.1 and Pax6.2 can act as transcriptional activators with Pax6.2 being more efficient than Pax6.1. PMID:18282108 Sequencing of sri homozygotes and heterozygotes identified a leucine to proline missense mutation in a highly conserved residue of the pax6b homeodomain (Figures 1B, S1B, and S1C). |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IDA PMID:9831649 Zebrafish contains two pax6 genes involved in eye developmen... | ACCEPT | Summary: pax6b encodes a paired/homeodomain DNA-binding transcription factor with directly measured transactivation activity. Reason: Both zebrafish Pax6 co-orthologues retain complete paired domains and homeodomains and activate paired-domain (CD19) and homeodomain (P3) reporter targets at indistinguishable levels in the same assay (PMID:18282108); both act as transcriptional activators and both induce ectopic eyes in Drosophila (PMID:9831649). The molecular function is therefore conserved in both copies and is correctly shared across the pair. The sunrise L244P homeodomain mutation reduces DNA binding and abolishes P3 activation, confirming that the activity depends on the DNA-binding domains. Supporting Evidence: PMID:18282108 Activation by the two wild type co-orthologues through the P3 homeodomain target [45] (Figure 1D), or the CD19 paired domain target [46] (Figure 1E), was not significantly different, in contrast to the original observations by Nornes et al [43]. PMID:9831649 Both Pax6.1 and Pax6.2 can act as transcriptional activators with Pax6.2 being more efficient than Pax6.1. PMID:18282108 Sequencing of sri homozygotes and heterozygotes identified a leucine to proline missense mutation in a highly conserved residue of the pax6b homeodomain (Figures 1B, S1B, and S1C). |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IEA GO_REF:0000002 | ACCEPT | Summary: pax6b encodes a paired/homeodomain DNA-binding transcription factor with directly measured transactivation activity. Reason: Both zebrafish Pax6 co-orthologues retain complete paired domains and homeodomains and activate paired-domain (CD19) and homeodomain (P3) reporter targets at indistinguishable levels in the same assay (PMID:18282108); both act as transcriptional activators and both induce ectopic eyes in Drosophila (PMID:9831649). The molecular function is therefore conserved in both copies and is correctly shared across the pair. The sunrise L244P homeodomain mutation reduces DNA binding and abolishes P3 activation, confirming that the activity depends on the DNA-binding domains. Supporting Evidence: PMID:18282108 Activation by the two wild type co-orthologues through the P3 homeodomain target [45] (Figure 1D), or the CD19 paired domain target [46] (Figure 1E), was not significantly different, in contrast to the original observations by Nornes et al [43]. PMID:9831649 Both Pax6.1 and Pax6.2 can act as transcriptional activators with Pax6.2 being more efficient than Pax6.1. PMID:18282108 Sequencing of sri homozygotes and heterozygotes identified a leucine to proline missense mutation in a highly conserved residue of the pax6b homeodomain (Figures 1B, S1B, and S1C). |
| GO:0001654 eye development | IMP PMID:18282108 Subfunctionalization of duplicated zebrafish pax6 genes by c... | ACCEPT | Summary: pax6b sunrise mutants and pax6b morphants have small eyes with lens and cornea defects. Reason: sunrise (pax6b L244P) homozygotes show a fully penetrant microphthalmia with abnormal lens and cornea; two pax6b morpholinos give a more severe reduction in eye size (PMID:18282108). Eye development is a core, ancestral Pax6 role shared with pax6a; the milder phenotype than in mammals reflects role-sharing with pax6a. Supporting Evidence: PMID:18282108 Sequencing of sri homozygotes and heterozygotes identified a leucine to proline missense mutation in a highly conserved residue of the pax6b homeodomain (Figures 1B, S1B, and S1C). PMID:18282108 First, pax6b morpholino injections, using two different morpholinos, resulted in reduced eye size, a phenotype overlapping the sri phenotype, but somewhat more severe, as total eye size reduction (Figure 3A and 3B) rather than just small lens size [27] (Figure 1A) was observed. PMID:18282108 The mild phenotype emphasizes role-sharing between the co-orthologues. |
| GO:0001654 eye development | IMP PMID:18282108 Subfunctionalization of duplicated zebrafish pax6 genes by c... | ACCEPT | Summary: pax6b sunrise mutants and pax6b morphants have small eyes with lens and cornea defects. Reason: sunrise (pax6b L244P) homozygotes show a fully penetrant microphthalmia with abnormal lens and cornea; two pax6b morpholinos give a more severe reduction in eye size (PMID:18282108). Eye development is a core, ancestral Pax6 role shared with pax6a; the milder phenotype than in mammals reflects role-sharing with pax6a. Supporting Evidence: PMID:18282108 Sequencing of sri homozygotes and heterozygotes identified a leucine to proline missense mutation in a highly conserved residue of the pax6b homeodomain (Figures 1B, S1B, and S1C). PMID:18282108 First, pax6b morpholino injections, using two different morpholinos, resulted in reduced eye size, a phenotype overlapping the sri phenotype, but somewhat more severe, as total eye size reduction (Figure 3A and 3B) rather than just small lens size [27] (Figure 1A) was observed. PMID:18282108 The mild phenotype emphasizes role-sharing between the co-orthologues. |
| GO:0001654 eye development | IMP PMID:18282108 Subfunctionalization of duplicated zebrafish pax6 genes by c... | ACCEPT | Summary: pax6b sunrise mutants and pax6b morphants have small eyes with lens and cornea defects. Reason: sunrise (pax6b L244P) homozygotes show a fully penetrant microphthalmia with abnormal lens and cornea; two pax6b morpholinos give a more severe reduction in eye size (PMID:18282108). Eye development is a core, ancestral Pax6 role shared with pax6a; the milder phenotype than in mammals reflects role-sharing with pax6a. Supporting Evidence: PMID:18282108 Sequencing of sri homozygotes and heterozygotes identified a leucine to proline missense mutation in a highly conserved residue of the pax6b homeodomain (Figures 1B, S1B, and S1C). PMID:18282108 First, pax6b morpholino injections, using two different morpholinos, resulted in reduced eye size, a phenotype overlapping the sri phenotype, but somewhat more severe, as total eye size reduction (Figure 3A and 3B) rather than just small lens size [27] (Figure 1A) was observed. PMID:18282108 The mild phenotype emphasizes role-sharing between the co-orthologues. |
| GO:0001755 neural crest cell migration | IGI PMID:32555736 Pax6 organizes the anterior eye segment by guiding two disti... | KEEP AS NON CORE | Summary: pax6a/pax6b compound mutants misroute two periocular neural crest populations. Reason: Supported by compound-mutant analysis with a gene-dose-dependent effect (PMID:32555736). The role is partly indirect (via the pax6-dependent lens and guidance cues), and it is shared with pax6a, whose equivalent ZFIN annotation is missing from the Swiss-Prot pax6a entry. Supporting Evidence: PMID:32555736 By analysing zebrafish pax6a/b compound mutants presenting anterior segment dysgenesis, we demonstrate that Pax6a/b guide the two NC populations to distinct proximodistal locations. PMID:32555736 Taken together, our data are consistent with a gene number dependent effect of pax6a/b on the migration of the two distinct waves of NC cells. |
| GO:0002088 lens development in camera-type eye | IMP PMID:17397257 Hsp90 selectively modulates phenotype in vertebrate developm... | ACCEPT | Summary: Hsp90 inhibition worsens lens size reduction in sunrise pax6b mutants. Reason: sunrise homozygotes have reduced lens size relative to retina, worsened by Hsp90 inhibition (PMID:17397257). Lens development is a core pax6b function (also PMID:20177065). Supporting Evidence: PMID:17397257 Under these conditions the severity of the recessive eye phenotype in sunrise, caused by a pax6b mutation, was increased PMID:17397257 Upon Hsp90 functional reduction, lens size relative to the area of the retina was significantly decreased in homozygous sri embryos while homozygous dre remained unaltered (Figure 3I; Table 2). PMID:20177065 Crosses between pax6b sa0086 carrier fish generated homozygous mutant embryos, all displaying severe lens defects |
| GO:0002089 lens morphogenesis in camera-type eye | IMP PMID:20177065 The Pax6b homeodomain is dispensable for pancreatic endocrin... | ACCEPT | Summary: pax6b null mutants and pax6b morphants (including homeodomain-deleting splice morpholinos) have strongly affected lens formation. Reason: All pax6b sa0086 (Y109*) homozygotes display severe lens defects, and deletion of the Pax6b homeodomain strongly affects lens formation while leaving the pancreas intact (PMID:20177065). The lens requires the homeodomain; the pancreas does not. Supporting Evidence: PMID:20177065 Crosses between pax6b sa0086 carrier fish generated homozygous mutant embryos, all displaying severe lens defects PMID:20177065 we show that deletion of the Pax6b homeodomain in zebrafish embryos does not disturb pancreas development, whereas lens formation is strongly affected. |
| GO:0002089 lens morphogenesis in camera-type eye | IMP PMID:20177065 The Pax6b homeodomain is dispensable for pancreatic endocrin... | ACCEPT | Summary: pax6b null mutants and pax6b morphants (including homeodomain-deleting splice morpholinos) have strongly affected lens formation. Reason: All pax6b sa0086 (Y109*) homozygotes display severe lens defects, and deletion of the Pax6b homeodomain strongly affects lens formation while leaving the pancreas intact (PMID:20177065). The lens requires the homeodomain; the pancreas does not. Supporting Evidence: PMID:20177065 Crosses between pax6b sa0086 carrier fish generated homozygous mutant embryos, all displaying severe lens defects PMID:20177065 we show that deletion of the Pax6b homeodomain in zebrafish embryos does not disturb pancreas development, whereas lens formation is strongly affected. |
| GO:0002089 lens morphogenesis in camera-type eye | IMP PMID:20177065 The Pax6b homeodomain is dispensable for pancreatic endocrin... | ACCEPT | Summary: pax6b null mutants and pax6b morphants (including homeodomain-deleting splice morpholinos) have strongly affected lens formation. Reason: All pax6b sa0086 (Y109*) homozygotes display severe lens defects, and deletion of the Pax6b homeodomain strongly affects lens formation while leaving the pancreas intact (PMID:20177065). The lens requires the homeodomain; the pancreas does not. Supporting Evidence: PMID:20177065 Crosses between pax6b sa0086 carrier fish generated homozygous mutant embryos, all displaying severe lens defects PMID:20177065 we show that deletion of the Pax6b homeodomain in zebrafish embryos does not disturb pancreas development, whereas lens formation is strongly affected. |
| GO:0002089 lens morphogenesis in camera-type eye | IMP PMID:20177065 The Pax6b homeodomain is dispensable for pancreatic endocrin... | ACCEPT | Summary: pax6b null mutants and pax6b morphants (including homeodomain-deleting splice morpholinos) have strongly affected lens formation. Reason: All pax6b sa0086 (Y109*) homozygotes display severe lens defects, and deletion of the Pax6b homeodomain strongly affects lens formation while leaving the pancreas intact (PMID:20177065). The lens requires the homeodomain; the pancreas does not. Supporting Evidence: PMID:20177065 Crosses between pax6b sa0086 carrier fish generated homozygous mutant embryos, all displaying severe lens defects PMID:20177065 we show that deletion of the Pax6b homeodomain in zebrafish embryos does not disturb pancreas development, whereas lens formation is strongly affected. |
| GO:0002089 lens morphogenesis in camera-type eye | IMP PMID:20177065 The Pax6b homeodomain is dispensable for pancreatic endocrin... | ACCEPT | Summary: pax6b null mutants and pax6b morphants (including homeodomain-deleting splice morpholinos) have strongly affected lens formation. Reason: All pax6b sa0086 (Y109*) homozygotes display severe lens defects, and deletion of the Pax6b homeodomain strongly affects lens formation while leaving the pancreas intact (PMID:20177065). The lens requires the homeodomain; the pancreas does not. Supporting Evidence: PMID:20177065 Crosses between pax6b sa0086 carrier fish generated homozygous mutant embryos, all displaying severe lens defects PMID:20177065 we show that deletion of the Pax6b homeodomain in zebrafish embryos does not disturb pancreas development, whereas lens formation is strongly affected. |
| GO:0003309 type B pancreatic cell differentiation | IBA GO_REF:0000033 | ACCEPT | Summary: IBA transfer of beta-cell differentiation; confirmed experimentally for pax6b. Reason: The IBA is consistent with pax6b's own IMP evidence (PMID:20177065, PMID:32867764); pax6b appearing among the IBA sources reflects experimental grounding on the target itself. Within the zebrafish pair, pax6b is the only copy expressed in the pancreas. Supporting Evidence: PMID:20177065 We show here that pax6b does play an essential role in pancreatic endocrine cell differentiation, as revealed by the phenotype of a novel zebrafish pax6b null mutant and of embryos injected with pax6b morpholinos. PMID:18282108 only pax6b is expressed in the pancreas isolated from 6 month old wild type and sri/sri fish, while eyes from the same individuals express both pax6a and pax6b |
| GO:0003309 type B pancreatic cell differentiation | IMP PMID:20177065 The Pax6b homeodomain is dispensable for pancreatic endocrin... | ACCEPT | Summary: pax6b is required for pancreatic beta-cell differentiation; pax6b-deficient embryos have almost no beta cells. Reason: Null mutant (sa0086) and three morpholinos give near-absence of beta cells (PMID:20177065), confirmed by RNA-seq of purified pancreatic endocrine cells (PMID:32867764). pax6b is the only pax6 copy expressed in the pancreas (PMID:18282108, PMID:18485195), so in zebrafish this ancestral PAX6 role is pax6b-specific. Supporting Evidence: PMID:20177065 We show here that pax6b does play an essential role in pancreatic endocrine cell differentiation, as revealed by the phenotype of a novel zebrafish pax6b null mutant and of embryos injected with pax6b morpholinos. PMID:20177065 Pax6b-depleted embryos have almost no beta cells, a strongly reduced number of delta cells, and a significant increase of epsilon cells. PMID:32867764 pax6b loss-of-function does not affect the total number of EECs and PECs but instead disrupts the balance between endocrine cell subtypes, leading to an increase of ghrelin- and motilin-like-expressing cells in both the intestine and pancreas at the expense of other endocrine cells such as beta and delta cells in the pancreas and pyyb-expressing cells in the intestine. PMID:18282108 only pax6b is expressed in the pancreas isolated from 6 month old wild type and sri/sri fish, while eyes from the same individuals express both pax6a and pax6b |
| GO:0003309 type B pancreatic cell differentiation | IMP PMID:20177065 The Pax6b homeodomain is dispensable for pancreatic endocrin... | ACCEPT | Summary: pax6b is required for pancreatic beta-cell differentiation; pax6b-deficient embryos have almost no beta cells. Reason: Null mutant (sa0086) and three morpholinos give near-absence of beta cells (PMID:20177065), confirmed by RNA-seq of purified pancreatic endocrine cells (PMID:32867764). pax6b is the only pax6 copy expressed in the pancreas (PMID:18282108, PMID:18485195), so in zebrafish this ancestral PAX6 role is pax6b-specific. Supporting Evidence: PMID:20177065 We show here that pax6b does play an essential role in pancreatic endocrine cell differentiation, as revealed by the phenotype of a novel zebrafish pax6b null mutant and of embryos injected with pax6b morpholinos. PMID:20177065 Pax6b-depleted embryos have almost no beta cells, a strongly reduced number of delta cells, and a significant increase of epsilon cells. PMID:32867764 pax6b loss-of-function does not affect the total number of EECs and PECs but instead disrupts the balance between endocrine cell subtypes, leading to an increase of ghrelin- and motilin-like-expressing cells in both the intestine and pancreas at the expense of other endocrine cells such as beta and delta cells in the pancreas and pyyb-expressing cells in the intestine. PMID:18282108 only pax6b is expressed in the pancreas isolated from 6 month old wild type and sri/sri fish, while eyes from the same individuals express both pax6a and pax6b |
| GO:0003309 type B pancreatic cell differentiation | IMP PMID:20177065 The Pax6b homeodomain is dispensable for pancreatic endocrin... | ACCEPT | Summary: pax6b is required for pancreatic beta-cell differentiation; pax6b-deficient embryos have almost no beta cells. Reason: Null mutant (sa0086) and three morpholinos give near-absence of beta cells (PMID:20177065), confirmed by RNA-seq of purified pancreatic endocrine cells (PMID:32867764). pax6b is the only pax6 copy expressed in the pancreas (PMID:18282108, PMID:18485195), so in zebrafish this ancestral PAX6 role is pax6b-specific. Supporting Evidence: PMID:20177065 We show here that pax6b does play an essential role in pancreatic endocrine cell differentiation, as revealed by the phenotype of a novel zebrafish pax6b null mutant and of embryos injected with pax6b morpholinos. PMID:20177065 Pax6b-depleted embryos have almost no beta cells, a strongly reduced number of delta cells, and a significant increase of epsilon cells. PMID:32867764 pax6b loss-of-function does not affect the total number of EECs and PECs but instead disrupts the balance between endocrine cell subtypes, leading to an increase of ghrelin- and motilin-like-expressing cells in both the intestine and pancreas at the expense of other endocrine cells such as beta and delta cells in the pancreas and pyyb-expressing cells in the intestine. PMID:18282108 only pax6b is expressed in the pancreas isolated from 6 month old wild type and sri/sri fish, while eyes from the same individuals express both pax6a and pax6b |
| GO:0003309 type B pancreatic cell differentiation | IMP PMID:20177065 The Pax6b homeodomain is dispensable for pancreatic endocrin... | ACCEPT | Summary: pax6b is required for pancreatic beta-cell differentiation; pax6b-deficient embryos have almost no beta cells. Reason: Null mutant (sa0086) and three morpholinos give near-absence of beta cells (PMID:20177065), confirmed by RNA-seq of purified pancreatic endocrine cells (PMID:32867764). pax6b is the only pax6 copy expressed in the pancreas (PMID:18282108, PMID:18485195), so in zebrafish this ancestral PAX6 role is pax6b-specific. Supporting Evidence: PMID:20177065 We show here that pax6b does play an essential role in pancreatic endocrine cell differentiation, as revealed by the phenotype of a novel zebrafish pax6b null mutant and of embryos injected with pax6b morpholinos. PMID:20177065 Pax6b-depleted embryos have almost no beta cells, a strongly reduced number of delta cells, and a significant increase of epsilon cells. PMID:32867764 pax6b loss-of-function does not affect the total number of EECs and PECs but instead disrupts the balance between endocrine cell subtypes, leading to an increase of ghrelin- and motilin-like-expressing cells in both the intestine and pancreas at the expense of other endocrine cells such as beta and delta cells in the pancreas and pyyb-expressing cells in the intestine. PMID:18282108 only pax6b is expressed in the pancreas isolated from 6 month old wild type and sri/sri fish, while eyes from the same individuals express both pax6a and pax6b |
| GO:0003309 type B pancreatic cell differentiation | IMP PMID:20177065 The Pax6b homeodomain is dispensable for pancreatic endocrin... | ACCEPT | Summary: pax6b is required for pancreatic beta-cell differentiation; pax6b-deficient embryos have almost no beta cells. Reason: Null mutant (sa0086) and three morpholinos give near-absence of beta cells (PMID:20177065), confirmed by RNA-seq of purified pancreatic endocrine cells (PMID:32867764). pax6b is the only pax6 copy expressed in the pancreas (PMID:18282108, PMID:18485195), so in zebrafish this ancestral PAX6 role is pax6b-specific. Supporting Evidence: PMID:20177065 We show here that pax6b does play an essential role in pancreatic endocrine cell differentiation, as revealed by the phenotype of a novel zebrafish pax6b null mutant and of embryos injected with pax6b morpholinos. PMID:20177065 Pax6b-depleted embryos have almost no beta cells, a strongly reduced number of delta cells, and a significant increase of epsilon cells. PMID:32867764 pax6b loss-of-function does not affect the total number of EECs and PECs but instead disrupts the balance between endocrine cell subtypes, leading to an increase of ghrelin- and motilin-like-expressing cells in both the intestine and pancreas at the expense of other endocrine cells such as beta and delta cells in the pancreas and pyyb-expressing cells in the intestine. PMID:18282108 only pax6b is expressed in the pancreas isolated from 6 month old wild type and sri/sri fish, while eyes from the same individuals express both pax6a and pax6b |
| GO:0003309 type B pancreatic cell differentiation | IMP PMID:32867764 Pancreatic and intestinal endocrine cells in zebrafish share... | ACCEPT | Summary: pax6b is required for pancreatic beta-cell differentiation; pax6b-deficient embryos have almost no beta cells. Reason: Null mutant (sa0086) and three morpholinos give near-absence of beta cells (PMID:20177065), confirmed by RNA-seq of purified pancreatic endocrine cells (PMID:32867764). pax6b is the only pax6 copy expressed in the pancreas (PMID:18282108, PMID:18485195), so in zebrafish this ancestral PAX6 role is pax6b-specific. Supporting Evidence: PMID:20177065 We show here that pax6b does play an essential role in pancreatic endocrine cell differentiation, as revealed by the phenotype of a novel zebrafish pax6b null mutant and of embryos injected with pax6b morpholinos. PMID:20177065 Pax6b-depleted embryos have almost no beta cells, a strongly reduced number of delta cells, and a significant increase of epsilon cells. PMID:32867764 pax6b loss-of-function does not affect the total number of EECs and PECs but instead disrupts the balance between endocrine cell subtypes, leading to an increase of ghrelin- and motilin-like-expressing cells in both the intestine and pancreas at the expense of other endocrine cells such as beta and delta cells in the pancreas and pyyb-expressing cells in the intestine. PMID:18282108 only pax6b is expressed in the pancreas isolated from 6 month old wild type and sri/sri fish, while eyes from the same individuals express both pax6a and pax6b |
| GO:0003310 pancreatic A cell differentiation | IMP PMID:20177065 The Pax6b homeodomain is dispensable for pancreatic endocrin... | ACCEPT | Summary: pax6b influences alpha-cell differentiation: partial knockdown increases alpha cells, while null mutants have misdifferentiated alpha cells. Reason: The phenotype is dose-dependent and variable: small morpholino doses raise alpha-cell number and glucagon, about 40% of null mutants have fewer alpha cells, and alpha cells in null mutants are misdifferentiated (PMID:20177065, PMID:32867764). pax6b clearly acts upstream of or within alpha-cell differentiation, although less decisively than for beta cells. Supporting Evidence: PMID:20177065 partial reduction of Pax6b function in zebrafish embryos performed by injection of small amounts of pax6b morpholinos caused a clear rise in alpha cell number and in glucagon expression PMID:20177065 On the other hand, the fact that Ξ± cell differentiation is not strongly affected in about 60% of pax6b sa0086 mutants indicates that a Pax6b-independent pathway may also be used to generate glucagon cells. PMID:32867764 Alpha cells are still generated in the pax6bsa0086 mutants, but these cells are misdifferentiated. |
| GO:0003310 pancreatic A cell differentiation | IMP PMID:20177065 The Pax6b homeodomain is dispensable for pancreatic endocrin... | ACCEPT | Summary: pax6b influences alpha-cell differentiation: partial knockdown increases alpha cells, while null mutants have misdifferentiated alpha cells. Reason: The phenotype is dose-dependent and variable: small morpholino doses raise alpha-cell number and glucagon, about 40% of null mutants have fewer alpha cells, and alpha cells in null mutants are misdifferentiated (PMID:20177065, PMID:32867764). pax6b clearly acts upstream of or within alpha-cell differentiation, although less decisively than for beta cells. Supporting Evidence: PMID:20177065 partial reduction of Pax6b function in zebrafish embryos performed by injection of small amounts of pax6b morpholinos caused a clear rise in alpha cell number and in glucagon expression PMID:20177065 On the other hand, the fact that Ξ± cell differentiation is not strongly affected in about 60% of pax6b sa0086 mutants indicates that a Pax6b-independent pathway may also be used to generate glucagon cells. PMID:32867764 Alpha cells are still generated in the pax6bsa0086 mutants, but these cells are misdifferentiated. |
| GO:0003310 pancreatic A cell differentiation | IMP PMID:32867764 Pancreatic and intestinal endocrine cells in zebrafish share... | ACCEPT | Summary: pax6b influences alpha-cell differentiation: partial knockdown increases alpha cells, while null mutants have misdifferentiated alpha cells. Reason: The phenotype is dose-dependent and variable: small morpholino doses raise alpha-cell number and glucagon, about 40% of null mutants have fewer alpha cells, and alpha cells in null mutants are misdifferentiated (PMID:20177065, PMID:32867764). pax6b clearly acts upstream of or within alpha-cell differentiation, although less decisively than for beta cells. Supporting Evidence: PMID:20177065 partial reduction of Pax6b function in zebrafish embryos performed by injection of small amounts of pax6b morpholinos caused a clear rise in alpha cell number and in glucagon expression PMID:20177065 On the other hand, the fact that Ξ± cell differentiation is not strongly affected in about 60% of pax6b sa0086 mutants indicates that a Pax6b-independent pathway may also be used to generate glucagon cells. PMID:32867764 Alpha cells are still generated in the pax6bsa0086 mutants, but these cells are misdifferentiated. |
| GO:0003311 pancreatic D cell differentiation | IMP PMID:20177065 The Pax6b homeodomain is dispensable for pancreatic endocrin... | ACCEPT | Summary: pax6b-deficient embryos have strongly reduced delta cells. Reason: Null mutants and morphants have a strongly reduced number of delta cells (PMID:20177065), and delta-cell genes are downregulated in sorted mutant endocrine cells (PMID:32867764). Supporting Evidence: PMID:20177065 Pax6b-depleted embryos have almost no beta cells, a strongly reduced number of delta cells, and a significant increase of epsilon cells. PMID:32867764 pax6b loss-of-function does not affect the total number of EECs and PECs but instead disrupts the balance between endocrine cell subtypes, leading to an increase of ghrelin- and motilin-like-expressing cells in both the intestine and pancreas at the expense of other endocrine cells such as beta and delta cells in the pancreas and pyyb-expressing cells in the intestine. |
| GO:0003311 pancreatic D cell differentiation | IMP PMID:20177065 The Pax6b homeodomain is dispensable for pancreatic endocrin... | ACCEPT | Summary: pax6b-deficient embryos have strongly reduced delta cells. Reason: Null mutants and morphants have a strongly reduced number of delta cells (PMID:20177065), and delta-cell genes are downregulated in sorted mutant endocrine cells (PMID:32867764). Supporting Evidence: PMID:20177065 Pax6b-depleted embryos have almost no beta cells, a strongly reduced number of delta cells, and a significant increase of epsilon cells. PMID:32867764 pax6b loss-of-function does not affect the total number of EECs and PECs but instead disrupts the balance between endocrine cell subtypes, leading to an increase of ghrelin- and motilin-like-expressing cells in both the intestine and pancreas at the expense of other endocrine cells such as beta and delta cells in the pancreas and pyyb-expressing cells in the intestine. |
| GO:0003311 pancreatic D cell differentiation | IMP PMID:20177065 The Pax6b homeodomain is dispensable for pancreatic endocrin... | ACCEPT | Summary: pax6b-deficient embryos have strongly reduced delta cells. Reason: Null mutants and morphants have a strongly reduced number of delta cells (PMID:20177065), and delta-cell genes are downregulated in sorted mutant endocrine cells (PMID:32867764). Supporting Evidence: PMID:20177065 Pax6b-depleted embryos have almost no beta cells, a strongly reduced number of delta cells, and a significant increase of epsilon cells. PMID:32867764 pax6b loss-of-function does not affect the total number of EECs and PECs but instead disrupts the balance between endocrine cell subtypes, leading to an increase of ghrelin- and motilin-like-expressing cells in both the intestine and pancreas at the expense of other endocrine cells such as beta and delta cells in the pancreas and pyyb-expressing cells in the intestine. |
| GO:0003311 pancreatic D cell differentiation | IMP PMID:20177065 The Pax6b homeodomain is dispensable for pancreatic endocrin... | ACCEPT | Summary: pax6b-deficient embryos have strongly reduced delta cells. Reason: Null mutants and morphants have a strongly reduced number of delta cells (PMID:20177065), and delta-cell genes are downregulated in sorted mutant endocrine cells (PMID:32867764). Supporting Evidence: PMID:20177065 Pax6b-depleted embryos have almost no beta cells, a strongly reduced number of delta cells, and a significant increase of epsilon cells. PMID:32867764 pax6b loss-of-function does not affect the total number of EECs and PECs but instead disrupts the balance between endocrine cell subtypes, leading to an increase of ghrelin- and motilin-like-expressing cells in both the intestine and pancreas at the expense of other endocrine cells such as beta and delta cells in the pancreas and pyyb-expressing cells in the intestine. |
| GO:0003311 pancreatic D cell differentiation | IMP PMID:20177065 The Pax6b homeodomain is dispensable for pancreatic endocrin... | ACCEPT | Summary: pax6b-deficient embryos have strongly reduced delta cells. Reason: Null mutants and morphants have a strongly reduced number of delta cells (PMID:20177065), and delta-cell genes are downregulated in sorted mutant endocrine cells (PMID:32867764). Supporting Evidence: PMID:20177065 Pax6b-depleted embryos have almost no beta cells, a strongly reduced number of delta cells, and a significant increase of epsilon cells. PMID:32867764 pax6b loss-of-function does not affect the total number of EECs and PECs but instead disrupts the balance between endocrine cell subtypes, leading to an increase of ghrelin- and motilin-like-expressing cells in both the intestine and pancreas at the expense of other endocrine cells such as beta and delta cells in the pancreas and pyyb-expressing cells in the intestine. |
| GO:0003311 pancreatic D cell differentiation | IMP PMID:32867764 Pancreatic and intestinal endocrine cells in zebrafish share... | ACCEPT | Summary: pax6b-deficient embryos have strongly reduced delta cells. Reason: Null mutants and morphants have a strongly reduced number of delta cells (PMID:20177065), and delta-cell genes are downregulated in sorted mutant endocrine cells (PMID:32867764). Supporting Evidence: PMID:20177065 Pax6b-depleted embryos have almost no beta cells, a strongly reduced number of delta cells, and a significant increase of epsilon cells. PMID:32867764 pax6b loss-of-function does not affect the total number of EECs and PECs but instead disrupts the balance between endocrine cell subtypes, leading to an increase of ghrelin- and motilin-like-expressing cells in both the intestine and pancreas at the expense of other endocrine cells such as beta and delta cells in the pancreas and pyyb-expressing cells in the intestine. |
| GO:0003677 DNA binding | IEA GO_REF:0000120 | ACCEPT | Summary: DNA binding; correct but general. Reason: Broad electronic term consistent with the more specific GO:0000978; pax6b binds P2/P3 homeodomain sites (PMID:18282108). Supporting Evidence: PMID:18282108 Sequencing of sri homozygotes and heterozygotes identified a leucine to proline missense mutation in a highly conserved residue of the pax6b homeodomain (Figures 1B, S1B, and S1C). |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Nuclear localization expected for a sequence-specific transcription factor. Reason: PAX6 family transcription factors act in the nucleus; consistent with demonstrated transactivation (PMID:18282108). Supporting Evidence: PMID:18282108 Activation by the two wild type co-orthologues through the P3 homeodomain target [45] (Figure 1D), or the CD19 paired domain target [46] (Figure 1E), was not significantly different, in contrast to the original observations by Nornes et al [43]. |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: Nuclear localization expected for a sequence-specific transcription factor. Reason: PAX6 family transcription factors act in the nucleus; consistent with demonstrated transactivation (PMID:18282108). Supporting Evidence: PMID:18282108 Activation by the two wild type co-orthologues through the P3 homeodomain target [45] (Figure 1D), or the CD19 paired domain target [46] (Figure 1E), was not significantly different, in contrast to the original observations by Nornes et al [43]. |
| GO:0006351 DNA-templated transcription | IEA GO_REF:0000104 | MODIFY | Summary: UniRule-based annotation to DNA-templated transcription. Reason: pax6b is a sequence-specific transcription factor: it regulates transcription rather than carrying out the synthesis of RNA itself. The regulatory term is the appropriate process. Proposed replacements: regulation of transcription by RNA polymerase II Supporting Evidence: PMID:9831649 Both Pax6.1 and Pax6.2 can act as transcriptional activators with Pax6.2 being more efficient than Pax6.1. |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000120 | ACCEPT | Summary: pax6b regulates transcription as a DNA-binding transcription factor. Reason: Correct process for a transcription factor with demonstrated activator activity (PMID:9831649, PMID:18282108). Supporting Evidence: PMID:9831649 Both Pax6.1 and Pax6.2 can act as transcriptional activators with Pax6.2 being more efficient than Pax6.1. PMID:18282108 Activation by the two wild type co-orthologues through the P3 homeodomain target [45] (Figure 1D), or the CD19 paired domain target [46] (Figure 1E), was not significantly different, in contrast to the original observations by Nornes et al [43]. |
| GO:0006357 regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | ACCEPT | Summary: pax6b regulates transcription as a DNA-binding transcription factor. Reason: Correct process for a transcription factor with demonstrated activator activity (PMID:9831649, PMID:18282108). Supporting Evidence: PMID:9831649 Both Pax6.1 and Pax6.2 can act as transcriptional activators with Pax6.2 being more efficient than Pax6.1. PMID:18282108 Activation by the two wild type co-orthologues through the P3 homeodomain target [45] (Figure 1D), or the CD19 paired domain target [46] (Figure 1E), was not significantly different, in contrast to the original observations by Nornes et al [43]. |
| GO:0007420 brain development | IBA GO_REF:0000033 | ACCEPT | Summary: pax6b is expressed in restricted brain domains (dorsal diencephalon, MHB, hindbrain) and contributes to brain development jointly with pax6a. Reason: Correct at the ancestral node. pax6b has lost several brain-specific cis-elements and has a narrower brain expression than pax6a (PMID:18282108), but it keeps brain expression and takes part with pax6a in diencephalic and hindbrain patterning (PMID:24528677, PMID:17010333). Supporting Evidence: PMID:18282108 pax6b is the βminorβ co-orthologue, expressed in the developing eye (retina and early lens placode), and also in thin strips of dorsal diencephalon, at the midbrain-hindbrain boundary (MHB), and in the pancreas. PMID:18282108 This may be the situation where several brain-specific elements, with spatiotemporal overlap in expression pattern, have been lost from pax6b. PMID:24528677 Similar to the loss of Pax6 in mice, blockage of the function of both zebrafish homologues pax6a and pax6b by morpholino oligomers led to an expansion of the MDO shh expression domain |
| GO:0007423 sensory organ development | IBA GO_REF:0000033 | ACCEPT | Summary: pax6b is required for eye (lens, cornea, iris) development, a sensory organ. Reason: General but correct; supported by sunrise and null-mutant eye phenotypes (PMID:18282108, PMID:25692557). Supporting Evidence: PMID:18282108 Sequencing of sri homozygotes and heterozygotes identified a leucine to proline missense mutation in a highly conserved residue of the pax6b homeodomain (Figures 1B, S1B, and S1C). PMID:25692557 We also characterised homozygous pax6b mutants. Mutant embryos have a thick cornea, iris hypoplasia, a shallow anterior chamber and a small lens. |
| GO:0009952 anterior/posterior pattern specification | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Reduced pax6a and/or pax6b activity anteriorizes the hoxd4a expression border and malforms rhombomere boundaries. Reason: Supported by morpholino evidence (PMID:17010333; abstract only, curator's IMP deferred to), but a peripheral patterning role shared with pax6a. Supporting Evidence: PMID:17010333 Additionally, stage-matched zebrafish embryos having decreased pax6a and/or pax6b activity display malformed rhombomere boundaries and an anteriorized hoxd4a expression border. |
| GO:0009952 anterior/posterior pattern specification | IMP PMID:17010333 Stereospecificity and PAX6 function direct Hoxd4 neural enha... | KEEP AS NON CORE | Summary: Reduced pax6a and/or pax6b activity anteriorizes the hoxd4a expression border and malforms rhombomere boundaries. Reason: Supported by morpholino evidence (PMID:17010333; abstract only, curator's IMP deferred to), but a peripheral patterning role shared with pax6a. Supporting Evidence: PMID:17010333 Additionally, stage-matched zebrafish embryos having decreased pax6a and/or pax6b activity display malformed rhombomere boundaries and an anteriorized hoxd4a expression border. |
| GO:0010468 regulation of gene expression | IGI PMID:24528677 Pax6 regulates the formation of the habenular nuclei by cont... | KEEP AS NON CORE | Summary: Double knockdown of pax6a/pax6b changes expression of shh, otx5 and cxcr4b in the diencephalon. Reason: The observation is sound (PMID:24528677), but 'regulation of gene expression' is a very general term for a transcription factor; the informative content is captured by the transcription-factor MF and the epithalamus annotation. Supporting Evidence: PMID:24528677 Similar to the loss of Pax6 in mice, blockage of the function of both zebrafish homologues pax6a and pax6b by morpholino oligomers led to an expansion of the MDO shh expression domain |
| GO:0021538 epithalamus development | IGI PMID:24528677 Pax6 regulates the formation of the habenular nuclei by cont... | KEEP AS NON CORE | Summary: Double pax6a/pax6b knockdown expands MDO shh expression and disrupts epithalamus formation. Reason: The IGI is based on combined knockdown of both co-orthologues (PMID:24528677), so it establishes a joint Pax6 requirement. A later study showed that pax6b null mutants have normal habenular markers while pax6a knockdown abolishes them (PMID:27387288), so the epithalamic role rests mainly with pax6a. Kept, as non-core for pax6b. Supporting Evidence: PMID:24528677 Similar to the loss of Pax6 in mice, blockage of the function of both zebrafish homologues pax6a and pax6b by morpholino oligomers led to an expansion of the MDO shh expression domain PMID:24528677 we show that pax6 controls the formation of the epithalamus mostly via the regulation of MDO shh expression in zebrafish. PMID:27387288 Homozygous pax6bsa86 mutant embryos display cxcr4b and brn3a expression in the habenulae largely indistinguishable from that of wild type siblings (Fig 2A, 2B, 2E and 2F). |
| GO:0030154 cell differentiation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: General term; pax6b acts in differentiation of pancreatic endocrine, enteroendocrine and ocular cells. Reason: Correct but uninformative; specific cell differentiation terms are annotated separately. Supporting Evidence: PMID:20177065 We show here that pax6b does play an essential role in pancreatic endocrine cell differentiation, as revealed by the phenotype of a novel zebrafish pax6b null mutant and of embryos injected with pax6b morpholinos. |
| GO:0030900 forebrain development | IBA GO_REF:0000033 | ACCEPT | Summary: pax6b is expressed in dorsal diencephalon and telencephalon-directed enhancers, and participates with pax6a in forebrain development. Reason: The IBA is consistent with pax6b expression in the dorsal diencephalon (PMID:18282108) and with the double-knockdown diencephalic phenotype (PMID:24528677). The main forebrain role in zebrafish sits with pax6a. Supporting Evidence: PMID:18282108 pax6b is the βminorβ co-orthologue, expressed in the developing eye (retina and early lens placode), and also in thin strips of dorsal diencephalon, at the midbrain-hindbrain boundary (MHB), and in the pancreas. PMID:24528677 Similar to the loss of Pax6 in mice, blockage of the function of both zebrafish homologues pax6a and pax6b by morpholino oligomers led to an expansion of the MDO shh expression domain |
| GO:0030902 hindbrain development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: pax6b is expressed in hindbrain and knockdown affected rhombomere boundaries. Reason: pax6b hindbrain expression increases by 32 hpf (PMID:18282108) and pax6a/pax6b knockdown malforms rhombomere boundaries (PMID:17010333). Peripheral, and shared with pax6a. Supporting Evidence: PMID:17010333 Additionally, stage-matched zebrafish embryos having decreased pax6a and/or pax6b activity display malformed rhombomere boundaries and an anteriorized hoxd4a expression border. |
| GO:0030902 hindbrain development | IMP PMID:17010333 Stereospecificity and PAX6 function direct Hoxd4 neural enha... | KEEP AS NON CORE | Summary: pax6b is expressed in hindbrain and knockdown affected rhombomere boundaries. Reason: pax6b hindbrain expression increases by 32 hpf (PMID:18282108) and pax6a/pax6b knockdown malforms rhombomere boundaries (PMID:17010333). Peripheral, and shared with pax6a. Supporting Evidence: PMID:17010333 Additionally, stage-matched zebrafish embryos having decreased pax6a and/or pax6b activity display malformed rhombomere boundaries and an anteriorized hoxd4a expression border. |
| GO:0035883 enteroendocrine cell differentiation | IMP PMID:32867764 Pancreatic and intestinal endocrine cells in zebrafish share... | ACCEPT | Summary: pax6b loss disrupts the balance of enteroendocrine cell subtypes in the intestine. Reason: pax6b null mutants gain ghrelin/motilin-like-expressing cells at the expense of other subtypes such as pyyb cells, in both intestine and pancreas (PMID:32867764); the pax6b P0 promoter drives enteroendocrine expression (PMID:18485195). A pax6b-specific role in zebrafish, matching the ancestral PAX6 role in gut endocrine cells. Supporting Evidence: PMID:32867764 pax6b loss-of-function does not affect the total number of EECs and PECs but instead disrupts the balance between endocrine cell subtypes, leading to an increase of ghrelin- and motilin-like-expressing cells in both the intestine and pancreas at the expense of other endocrine cells such as beta and delta cells in the pancreas and pyyb-expressing cells in the intestine. PMID:18485195 We show that the pax6b P0 promoter targets expression to endocrine pancreatic cells and also to enteroendocrine cells, retinal neurons and the telencephalon of transgenic zebrafish. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:9831649 Zebrafish contains two pax6 genes involved in eye developmen... | ACCEPT | Summary: pax6b (Pax6.2) activates transcription in reporter assays. Reason: Directly shown (PMID:9831649); the later side-by-side assay found pax6a and pax6b equally active (PMID:18282108). Supporting Evidence: PMID:9831649 Both Pax6.1 and Pax6.2 can act as transcriptional activators with Pax6.2 being more efficient than Pax6.1. PMID:18282108 Activation by the two wild type co-orthologues through the P3 homeodomain target [45] (Figure 1D), or the CD19 paired domain target [46] (Figure 1E), was not significantly different, in contrast to the original observations by Nornes et al [43]. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IEA GO_REF:0000117 | ACCEPT | Summary: pax6b activates transcription from Pax6 target sites. Reason: Consistent with experimental activator data (PMID:9831649, PMID:18282108). Supporting Evidence: PMID:9831649 Both Pax6.1 and Pax6.2 can act as transcriptional activators with Pax6.2 being more efficient than Pax6.1. |
| GO:0048593 camera-type eye morphogenesis | IEA GO_REF:0000117 | ACCEPT | Summary: pax6b takes part in camera-type eye morphogenesis. Reason: pax6b mutants have small lens, thick cornea, iris hypoplasia and shallow anterior chamber (PMID:25692557). Supporting Evidence: PMID:25692557 We also characterised homozygous pax6b mutants. Mutant embryos have a thick cornea, iris hypoplasia, a shallow anterior chamber and a small lens. |
| GO:0060041 retina development in camera-type eye | IBA GO_REF:0000033 | ACCEPT | Summary: pax6b is expressed in the developing retina and contributes to retinal development together with pax6a. Reason: Retinal expression of pax6b is established (PMID:18282108); severe sunrise alleles show retinal malformation and double mutants lack the ganglion cell layer (PMID:32555736). Supporting Evidence: PMID:18282108 pax6b is the βminorβ co-orthologue, expressed in the developing eye (retina and early lens placode), and also in thin strips of dorsal diencephalon, at the midbrain-hindbrain boundary (MHB), and in the pancreas. PMID:32555736 In concordance with mouse homozygous pax6 mutant phenotypes, zebrafish pax6a-/-;pax6b-/- double homozygous mutants showed severe defects in distal eye structures, lacking the lens, iris, corneal endothelium and ganglion cell layer of the retina. |
| GO:0061303 cornea development in camera-type eye | IMP PMID:25692557 Molecular description of eye defects in the zebrafish Pax6b ... | ACCEPT | Summary: pax6b mutants have a thick cornea with disrupted corneal endothelium and loss of corneal epithelial gene expression. Reason: Directly shown in homozygous pax6b mutants (PMID:25692557). Supporting Evidence: PMID:25692557 We also characterised homozygous pax6b mutants. Mutant embryos have a thick cornea, iris hypoplasia, a shallow anterior chamber and a small lens. PMID:25692557 Lack of pax6b function leads to severe disturbance of the corneal gene regulatory programme. |
| GO:0090104 pancreatic epsilon cell differentiation | IMP PMID:20177065 The Pax6b homeodomain is dispensable for pancreatic endocrin... | ACCEPT | Summary: pax6b loss increases ghrelin-expressing epsilon cells at the expense of beta and delta cells. Reason: pax6b restricts the epsilon fate: its loss causes a significant increase of epsilon cells (PMID:20177065, PMID:32867764). The annotation (acts upstream of or within epsilon cell differentiation) correctly records involvement without implying promotion. Supporting Evidence: PMID:20177065 Pax6b-depleted embryos have almost no beta cells, a strongly reduced number of delta cells, and a significant increase of epsilon cells. PMID:32867764 Thus, these data also indicate an increase of epsilon cells in pax6bsa0086 mutant embryos. PMID:32867764 pax6b loss-of-function does not affect the total number of EECs and PECs but instead disrupts the balance between endocrine cell subtypes, leading to an increase of ghrelin- and motilin-like-expressing cells in both the intestine and pancreas at the expense of other endocrine cells such as beta and delta cells in the pancreas and pyyb-expressing cells in the intestine. |
| GO:0090104 pancreatic epsilon cell differentiation | IMP PMID:20177065 The Pax6b homeodomain is dispensable for pancreatic endocrin... | ACCEPT | Summary: pax6b loss increases ghrelin-expressing epsilon cells at the expense of beta and delta cells. Reason: pax6b restricts the epsilon fate: its loss causes a significant increase of epsilon cells (PMID:20177065, PMID:32867764). The annotation (acts upstream of or within epsilon cell differentiation) correctly records involvement without implying promotion. Supporting Evidence: PMID:20177065 Pax6b-depleted embryos have almost no beta cells, a strongly reduced number of delta cells, and a significant increase of epsilon cells. PMID:32867764 Thus, these data also indicate an increase of epsilon cells in pax6bsa0086 mutant embryos. PMID:32867764 pax6b loss-of-function does not affect the total number of EECs and PECs but instead disrupts the balance between endocrine cell subtypes, leading to an increase of ghrelin- and motilin-like-expressing cells in both the intestine and pancreas at the expense of other endocrine cells such as beta and delta cells in the pancreas and pyyb-expressing cells in the intestine. |
| GO:0090104 pancreatic epsilon cell differentiation | IMP PMID:20177065 The Pax6b homeodomain is dispensable for pancreatic endocrin... | ACCEPT | Summary: pax6b loss increases ghrelin-expressing epsilon cells at the expense of beta and delta cells. Reason: pax6b restricts the epsilon fate: its loss causes a significant increase of epsilon cells (PMID:20177065, PMID:32867764). The annotation (acts upstream of or within epsilon cell differentiation) correctly records involvement without implying promotion. Supporting Evidence: PMID:20177065 Pax6b-depleted embryos have almost no beta cells, a strongly reduced number of delta cells, and a significant increase of epsilon cells. PMID:32867764 Thus, these data also indicate an increase of epsilon cells in pax6bsa0086 mutant embryos. PMID:32867764 pax6b loss-of-function does not affect the total number of EECs and PECs but instead disrupts the balance between endocrine cell subtypes, leading to an increase of ghrelin- and motilin-like-expressing cells in both the intestine and pancreas at the expense of other endocrine cells such as beta and delta cells in the pancreas and pyyb-expressing cells in the intestine. |
| GO:0090104 pancreatic epsilon cell differentiation | IMP PMID:20177065 The Pax6b homeodomain is dispensable for pancreatic endocrin... | ACCEPT | Summary: pax6b loss increases ghrelin-expressing epsilon cells at the expense of beta and delta cells. Reason: pax6b restricts the epsilon fate: its loss causes a significant increase of epsilon cells (PMID:20177065, PMID:32867764). The annotation (acts upstream of or within epsilon cell differentiation) correctly records involvement without implying promotion. Supporting Evidence: PMID:20177065 Pax6b-depleted embryos have almost no beta cells, a strongly reduced number of delta cells, and a significant increase of epsilon cells. PMID:32867764 Thus, these data also indicate an increase of epsilon cells in pax6bsa0086 mutant embryos. PMID:32867764 pax6b loss-of-function does not affect the total number of EECs and PECs but instead disrupts the balance between endocrine cell subtypes, leading to an increase of ghrelin- and motilin-like-expressing cells in both the intestine and pancreas at the expense of other endocrine cells such as beta and delta cells in the pancreas and pyyb-expressing cells in the intestine. |
| GO:0090104 pancreatic epsilon cell differentiation | IMP PMID:20177065 The Pax6b homeodomain is dispensable for pancreatic endocrin... | ACCEPT | Summary: pax6b loss increases ghrelin-expressing epsilon cells at the expense of beta and delta cells. Reason: pax6b restricts the epsilon fate: its loss causes a significant increase of epsilon cells (PMID:20177065, PMID:32867764). The annotation (acts upstream of or within epsilon cell differentiation) correctly records involvement without implying promotion. Supporting Evidence: PMID:20177065 Pax6b-depleted embryos have almost no beta cells, a strongly reduced number of delta cells, and a significant increase of epsilon cells. PMID:32867764 Thus, these data also indicate an increase of epsilon cells in pax6bsa0086 mutant embryos. PMID:32867764 pax6b loss-of-function does not affect the total number of EECs and PECs but instead disrupts the balance between endocrine cell subtypes, leading to an increase of ghrelin- and motilin-like-expressing cells in both the intestine and pancreas at the expense of other endocrine cells such as beta and delta cells in the pancreas and pyyb-expressing cells in the intestine. |
| GO:0090104 pancreatic epsilon cell differentiation | IMP PMID:32867764 Pancreatic and intestinal endocrine cells in zebrafish share... | ACCEPT | Summary: pax6b loss increases ghrelin-expressing epsilon cells at the expense of beta and delta cells. Reason: pax6b restricts the epsilon fate: its loss causes a significant increase of epsilon cells (PMID:20177065, PMID:32867764). The annotation (acts upstream of or within epsilon cell differentiation) correctly records involvement without implying promotion. Supporting Evidence: PMID:20177065 Pax6b-depleted embryos have almost no beta cells, a strongly reduced number of delta cells, and a significant increase of epsilon cells. PMID:32867764 Thus, these data also indicate an increase of epsilon cells in pax6bsa0086 mutant embryos. PMID:32867764 pax6b loss-of-function does not affect the total number of EECs and PECs but instead disrupts the balance between endocrine cell subtypes, leading to an increase of ghrelin- and motilin-like-expressing cells in both the intestine and pancreas at the expense of other endocrine cells such as beta and delta cells in the pancreas and pyyb-expressing cells in the intestine. |
| GO:2000179 positive regulation of neural precursor cell proliferation | IMP PMID:20152834 Pax6a and Pax6b are required at different points in neuronal... | NEW | Summary: pax6b is required for the first division of Muller glia-derived neuronal progenitors during photoreceptor regeneration. Reason: pax6b knockdown in the light-damaged adult retina blocked the first division of neuronal progenitors without affecting Muller glia division (PMID:20152834). The same paper supports the (modified) pax6a annotation; the pax6b counterpart is missing from GOA because only the Swiss-Prot pax6a entry was annotated from this paper. Non-core (regeneration context). Supporting Evidence: PMID:20152834 Loss of Pax6b expression did not affect MΓΌller glial cell division, but blocked the subsequent first cell division of the neuronal progenitors. PMID:20152834 This work also defines distinct roles for Pax6a and Pax6b in regulating neuronal progenitor cell proliferation in the adult zebrafish retina |
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Download this section (compressed HTML)Q: Which Pax6b DNA-binding mode (paired domain alone, or the 5a isoform) drives pancreatic and enteroendocrine target genes, given that the homeodomain is dispensable there?
Suggested experts: Peers B, Manfroid I
Q: Is the mild sunrise eye phenotype partly buffered by pax6a, and does pax6a expression rise in pax6b null (sa0086) eyes?
Experiment: Express pax6a coding sequence from pax6b pancreatic enhancers (regions A/C) in pax6b sa0086 mutants and score beta, delta and epsilon cells.
Hypothesis: Pancreatic endocrine differentiation requires Pax6 protein of either copy, and pax6a would rescue pax6b loss if expressed in the pancreas.
Type: cross-rescue
Experiment: CUT&RUN for Pax6b in sorted wild-type and sunrise pancreatic endocrine cells.
Hypothesis: pax6b binds endocrine target enhancers through its paired domain.
Type: genome-wide DNA-binding profiling
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