zic1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0000977 RNA polymerase II transcription regulatory region sequence-specific DNA binding	IEA GO_REF:0000002	ACCEPT	Summary: Zic1 binds DNA sequence-specifically through its C2H2 zinc fingers. Frog Zic1 binds a conserved element upstream of snail1 in EMSA, competed by wild-type but not mutant oligonucleotide, and mouse Zic1 selects a GLI-like site. The InterPro GLI-like mapping is consistent with this. Reason: Direct frog EMSA evidence plus the conserved Zic/GLI zinc-finger DNA-binding mode support Pol II regulatory-region sequence-specific DNA binding. The parent is slightly broader than the IBA term but correct. Supporting Evidence: PMID:24360906 Similarly, we showed that Zic1 binds to snail1 putative oligonucleotide but not to the snail1 oligonucleotide mutated on the putative binding site (Figure 4E and not shown). PMID:11053430 The selected sequence was almost identical to the GLI binding sequence.
GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA GO_REF:0000033	ACCEPT	Summary: Zic1 binds DNA sequence-specifically through its C2H2 zinc fingers. Frog Zic1 binds a conserved element upstream of snail1 in EMSA, competed by wild-type but not mutant oligonucleotide, and mouse Zic1 selects a GLI-like site. Reason: The IBA node (PTN001803442) covers the GLI/Zic/Ci clade, whose members are experimentally established cis-regulatory DNA binders. Frog Zic1 itself binds the snail1 upstream element, so the inheritance is supported on the target. Supporting Evidence: PMID:24360906 Similarly, we showed that Zic1 binds to snail1 putative oligonucleotide but not to the snail1 oligonucleotide mutated on the putative binding site (Figure 4E and not shown). PMID:11053430 The selected sequence was almost identical to the GLI binding sequence.
GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding	IEA GO_REF:0000118	ACCEPT	Summary: Zic1 binds DNA sequence-specifically through its C2H2 zinc fingers. Frog Zic1 binds a conserved element upstream of snail1 in EMSA, competed by wild-type but not mutant oligonucleotide, and mouse Zic1 selects a GLI-like site. Reason: TreeGrafter transfer of the same family function; correct for Zic1. Supporting Evidence: PMID:24360906 Similarly, we showed that Zic1 binds to snail1 putative oligonucleotide but not to the snail1 oligonucleotide mutated on the putative binding site (Figure 4E and not shown).
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific	IBA GO_REF:0000033	ACCEPT	Summary: Zic1 is a DNA-binding transcription factor that activates Pol II target genes (snail1 directly; with Pax3, snail2, foxd3, twist1 and tfap2b). Reason: Correct family-level MF from the GLI/Zic PAINT node. Frog evidence (transcriptional activator, EMSA-validated snail1 element, cycloheximide-resistant induction) shows the activity is specifically activating; the activator child term GO:0001228 is proposed as NEW alongside. Supporting Evidence: PMID:9655809 opl encodes a transcriptional activator, with a carboxy terminal regulatory domain, which when removed increases opl activity. PMID:24360906 Firstly, the main known neural crest specifiers, snail1, snail2 and twist1, were highly and reproducibly activated either by Pax3 (snail2, twist1) or by Zic1 (snail1) in the presence of cycloheximide.
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific	IEA GO_REF:0000118	ACCEPT	Summary: Zic1 is a DNA-binding transcription factor that activates Pol II target genes (snail1 directly; with Pax3, snail2, foxd3, twist1 and tfap2b). Reason: TreeGrafter transfer of the same family MF; correct. Supporting Evidence: PMID:9655809 opl encodes a transcriptional activator, with a carboxy terminal regulatory domain, which when removed increases opl activity.
GO:0001840 neural plate development	IMP PMID:16871635 The Xfeb gene is directly upregulated by Zic1 during early n...	ACCEPT	Summary: Zic1 is one of the earliest neural plate genes. It is induced directly by BMP inhibition, is required with Zic3 for definitive neural fate, patterns the neural plate (e.g. through its direct target Xfeb) and partitions the lateral neural plate border into crest and preplacodal fates. Reason: Neural plate development is the right broad process for Zic1: every Zic1 output (neural fate, border specification, regionalization) is executed in the neural plate and its border. Zic1 does the work as a transcriptional activator of neural plate genes. The cited paper shows Zic1 directly upregulates Xfeb, a neural plate regionalizing factor. Supporting Evidence: PMID:16871635 The transcription factor Zic1 plays important roles in patterning the neural plate in early vertebrate development. PMID:16871635 We have identified a new direct downstream target gene of Zic1 that we have named Xfeb. PMID:16871635 Xfeb represses the hindbrain gene hoxB1 and the anterior neural gene otx2, suggesting that Xfeb is involved in regionalizing the neural plate, possibly by ensuring a posterior expression limit for otx2. PMID:19805078 Conversely, we found that zic1 can be activated by BMP inhibition in the absence of translation. PMID:19805078 Finally, Zic1 and Zic3 are required together for definitive neural fate acquisition, both in ectopic and endogenous situations.
GO:0003700 DNA-binding transcription factor activity	ISS GO_REF:0000024	ACCEPT	Summary: DNA-binding transcription factor activity transferred from mouse Zic1, which shows transcriptional activation in cultured cells. Reason: Correct but general; frog Zic1 is a transcriptional activator (see GO:0000981 rows and NEW GO:0001228). Supporting Evidence: PMID:9655809 opl encodes a transcriptional activator, with a carboxy terminal regulatory domain, which when removed increases opl activity. PMID:11053430 these results suggest that Zic proteins may act as transcriptional coactivators and that their function may be modulated by the GLI proteins and possibly by other cell type-specific cofactors.
GO:0005634 nucleus	IBA GO_REF:0000033	ACCEPT	Summary: Zic1 is a nuclear transcription factor. Reason: Nuclear localization is conserved across the GLI/Zic family and expected for a DNA-binding activator. Supporting Evidence: PMID:9655809 opl encodes a transcriptional activator, with a carboxy terminal regulatory domain, which when removed increases opl activity.
GO:0005634 nucleus	IDA PMID:9655809 Opl: a zinc finger protein that regulates neural determinati...	ACCEPT	Summary: Zic1 is a nuclear transcription factor. The original paper characterized Opl as a transcriptional activator; UniProt records nuclear localization from this paper. Reason: Experimental localization (abstract-only cache; the localization data is in the full text the curator read) consistent with its activity. Supporting Evidence: PMID:9655809 opl encodes a transcriptional activator, with a carboxy terminal regulatory domain, which when removed increases opl activity.
GO:0005634 nucleus	IEA GO_REF:0000120	ACCEPT	Summary: Zic1 is a nuclear transcription factor. Reason: Correct combined IEA. Supporting Evidence: PMID:9655809 opl encodes a transcriptional activator, with a carboxy terminal regulatory domain, which when removed increases opl activity.
GO:0005737 cytoplasm	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Cytoplasmic localization of Zic proteins has been seen in mammalian cultured cells when nuclear import is blocked by partners such as I-mfa. In frog gastrula cells Zic1 is reported nuclear. Reason: From a UniProt by-similarity SubCell line. Conditional cytoplasmic retention is plausible for Zic family proteins, but it is not where frog Zic1 does its work. Supporting Evidence: PMID:15207726 When Zic1-3 and I-mfa proteins were co-expressed in cultured cells, nuclear import of the Zic proteins was inhibited.
GO:0005737 cytoplasm	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Cytoplasmic localization of Zic proteins has been seen in mammalian cultured cells when nuclear import is blocked by partners such as I-mfa. In frog gastrula cells Zic1 is reported nuclear. Reason: ISS from mouse Zic1 (P46684), whose cytoplasmic evidence is I-mfa-mediated retention in cultured cells. A regulatory, non-core location. Supporting Evidence: PMID:15207726 When Zic1-3 and I-mfa proteins were co-expressed in cultured cells, nuclear import of the Zic proteins was inhibited.
GO:0006357 regulation of transcription by RNA polymerase II	IBA GO_REF:0000033	ACCEPT	Summary: Zic1 regulates Pol II transcription of neural plate and neural plate border target genes. Reason: Correct general BP from the PAINT node; specific activation is captured by GO:0045944 rows. Supporting Evidence: PMID:24360906 We demonstrated that the neural border specifiers Pax3 and Zic1 are direct upstream regulators of neural crest specifiers Snail1/2, Foxd3, Twist1, and Tfap2b.
GO:0006357 regulation of transcription by RNA polymerase II	IEA GO_REF:0000118	ACCEPT	Summary: Zic1 regulates Pol II transcription of neural plate and neural plate border target genes. Reason: Correct general BP (TreeGrafter). Supporting Evidence: PMID:24360906 We demonstrated that the neural border specifiers Pax3 and Zic1 are direct upstream regulators of neural crest specifiers Snail1/2, Foxd3, Twist1, and Tfap2b.
GO:0007417 central nervous system development	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Zic genes act in CNS development (dorsal neural tube, midbrain-hindbrain, cerebellum in mammals). Frog Zic1 is expressed in the dorsal neural tube and forebrain/midbrain at tailbud stages. Reason: The IBA (PTN008366297, Zic clade) is sound for the family and frog Zic1 is expressed and active in the later CNS. Relative to its core early role as a neural plate/border specifier, this later CNS role is non-core. Supporting Evidence: PMID:9655809 At the onset of gastrulation, opl is expressed throughout the presumptive neural plate, indicating that neural determination has begun at this stage while, by neurula, opl expression is restricted to the dorsal neural tube and neural crest. PMID:17330889 They are involved in development of neural tissues and the neural crest, in left-right axis patterning, in somite development, and in formation of the cerebellum.
GO:0014029 neural crest formation	IEA GO_REF:0000117	MODIFY	Summary: Zic1 is a neural plate border specifier. It is expressed in the lateral neural plate border before the crest specifiers and, with Pax3, is necessary and sufficient to establish the crest-forming border region. Reason: Electronic transfer of a border-specifier role (matches pax3-a and the other Xenopus Zic paralogs). GO:0014029 is proposed for obsoletion (projects/NEURAL_CREST_FORMATION_OBSOLETION.md): its definition describes forming the neural plate border region while its placement is under epithelial to mesenchymal transition. This gene's role is border formation, captured by the proposed term 'neural plate border formation' (NTR). Proposed replacements: neural plate border formation neural crest cell fate commitment Supporting Evidence: PMID:15843410 Pax3 and Zic1 are expressed in an overlapping manner in the presumptive neural crest area of the Xenopus gastrula, even prior to the onset of the expression of the early bona fide neural crest marker genes Foxd3 and Slug. PMID:24360908 Transcription factors pax3 and zic1 are among the earliest genes activated in NC progenitors, and they are both necessary and sufficient to promote NC fate.
GO:0014029 neural crest formation	IMP PMID:17409353 The activity of Pax3 and Zic1 regulates three distinct cell ...	MODIFY	Summary: Zic1 is a neural plate border specifier. It is expressed in the lateral neural plate border before the crest specifiers and, with Pax3, is necessary and sufficient to establish the crest-forming border region. Zic1 knockdown abolishes Snail2 induction and its combined activity with Pax3 specifies the neural crest. Reason: Full text: Zic1 MO abolishes crest (Snail2) induction, and Pax3+Zic1 together specify crest at the border while Zic1 alone gives preplacodal fate. Zic1 with Pax3 also directly induces crest fate (GO:0014034). GO:0014029 is proposed for obsoletion (projects/NEURAL_CREST_FORMATION_OBSOLETION.md): its definition describes forming the neural plate border region while its placement is under epithelial to mesenchymal transition. This gene's role is border formation, captured by the proposed term 'neural plate border formation' (NTR). Proposed replacements: neural plate border formation neural crest cell fate commitment Supporting Evidence: PMID:17409353 Using gain of function and knockdown approaches in whole embryos and animal explants, we demonstrate that Pax3 and Zic1 are necessary and sufficient to promote hatching gland and preplacodal fates, respectively, whereas their combined activity is essential to specify the neural crest. PMID:17409353 Snail2 induction in Noggin+Wnt-injected explants was abolished in the absence of Zic1 function PMID:17409353 Although in distinct regions of the ectoderm, Pax3 and Zic1 can independently promote HG and PE fates; in domain of the ectoderm where both factors are coexpressed, their combined activities specify the NC.
GO:0014029 neural crest formation	IMP PMID:9435279 Xenopus Zic-related-1 and Sox-2, two factors induced by chor...	MODIFY	Summary: Zic-r1 (Zic1) is an early chordin-induced neural gene that initiates neural and neuronal differentiation; its crest role is documented in companion papers. Reason: Abstract-only cache describes neural induction, not crest; the crest data the curator used must be in the full text, which we have not seen. The biology (Zic1 required for crest formation at the border) is well established by PMID:15843410, PMID:17409353 and PMID:24360906, so accepted deferring to the curator. Flagged in notes. The cached abstract reports only mRNA injection (gain-of-function); the role is carried forward because PMID:15843410 supplies loss-of-function evidence for the same gene. GO:0014029 is proposed for obsoletion (projects/NEURAL_CREST_FORMATION_OBSOLETION.md): its definition describes forming the neural plate border region while its placement is under epithelial to mesenchymal transition. This gene's role is border formation, captured by the proposed term 'neural plate border formation' (NTR). Proposed replacements: neural plate border formation neural crest cell fate commitment Supporting Evidence: PMID:9435279 Expression of the two genes is first detected widely in the prospective neuroectoderm at the beginning of gastrulation PMID:15843410 Loss-of-function studies in vivo and in the animal cap show that co-presence of Pax3 and Zic1 is essential for the initiation of neural crest differentiation.
GO:0014029 neural crest formation	IMP PMID:9655809 Opl: a zinc finger protein that regulates neural determinati...	MODIFY	Summary: Activated Opl (Zic1) induces neural crest and dorsal neural tube markers in animal caps and embryos. Reason: Gain-of-function supports Zic1 driving the crest-forming border program. GO:0014029 is proposed for obsoletion (projects/NEURAL_CREST_FORMATION_OBSOLETION.md): its definition describes forming the neural plate border region while its placement is under epithelial to mesenchymal transition. This gene's role is border formation, captured by the proposed term 'neural plate border formation' (NTR). Gain-of-function alone would be read as over-annotation (project rule, 2026-10-09); it is carried forward here only because loss-of-function evidence for the same gene (PMID:15843410, Zic1 MO) independently establishes the role. Proposed replacements: neural plate border formation neural crest cell fate commitment Supporting Evidence: PMID:9655809 the activated form of opl is able to induce neural crest and dorsal neural tube markers both in animal caps and whole embryos. PMID:9655809 At the onset of gastrulation, opl is expressed throughout the presumptive neural plate, indicating that neural determination has begun at this stage while, by neurula, opl expression is restricted to the dorsal neural tube and neural crest. PMID:15843410 Loss-of-function studies in vivo and in the animal cap show that co-presence of Pax3 and Zic1 is essential for the initiation of neural crest differentiation.
GO:0014029 neural crest formation	IMP PMID:9739105 Xenopus Zic family and its role in neural and neural crest d...	MODIFY	Summary: Zic1 overexpression enhances neural crest-derived tissue formation and induces crest markers in animal caps. Reason: Gain-of-function data; consistent with the border specifier role. The zic2-a and zic4 rows from the same overexpression work are marked over-annotated because those genes lack loss-of-function support. GO:0014029 is proposed for obsoletion (projects/NEURAL_CREST_FORMATION_OBSOLETION.md): its definition describes forming the neural plate border region while its placement is under epithelial to mesenchymal transition. This gene's role is border formation, captured by the proposed term 'neural plate border formation' (NTR). Gain-of-function alone would be read as over-annotation (project rule, 2026-10-09); it is carried forward here only because loss-of-function evidence for the same gene (PMID:15843410, Zic1 MO) independently establishes the role. Proposed replacements: neural plate border formation neural crest cell fate commitment Supporting Evidence: PMID:9739105 We observed enhanced neural and neural crest-derived tissue formation in the Zic1 or Zic2 overexpressed embryos and neural and neural crest marker induction in the Zic1 or Zic2 overexpressed animal cap explants. PMID:9739105 the Xenopus Zic family may act cooperatively in the initial phase of neural and neural crest development. PMID:15843410 Loss-of-function studies in vivo and in the animal cap show that co-presence of Pax3 and Zic1 is essential for the initiation of neural crest differentiation.
GO:0014033 neural crest cell differentiation	IMP PMID:9655809 Opl: a zinc finger protein that regulates neural determinati...	MODIFY	Summary: Activated Opl (Zic1) induces neural crest markers in ectoderm; the paper does not show Zic1 executing crest differentiation itself. Reason: Zic1 initiates the crest program (with Pax3); differentiation into derivatives is executed by downstream specifiers and effectors (sox8/9/10, snai2, twist1). Marker induction in caps is evidence for initiation/commitment, so GO:0014034 neural crest cell fate commitment is the better level (already on the gene from other papers). Proposed replacements: neural crest cell fate commitment Supporting Evidence: PMID:9655809 the activated form of opl is able to induce neural crest and dorsal neural tube markers both in animal caps and whole embryos. PMID:23509273 Thus, Pax3 and Zic1 cooperate and execute a transcriptional switch sufficient to activate full multipotent neural crest development and differentiation.
GO:0014034 neural crest cell fate commitment	IGI PMID:15843410 Neural crest determination by co-activation of Pax3 and Zic1...	ACCEPT	Summary: Pax3 and Zic1 together determine neural crest fate: their co-expression induces ectopic crest in ventral ectoderm and drives full crest determination, migration and differentiation; Zic1 directly activates the crest specifier snail1, and with Pax3 it activates snail2, foxd3, twist1, tfap2b and sox8. Reason: Core function. The IGI with Pax3 (Q645N4) captures exactly the cooperative switch. Zic1 does part of the work (DNA-binding activator of the specifier genes), so commitment-level annotation is justified. GO:0014036 is not added: it is part_of GO:0014034 and reserved by the project convention for the downstream specifiers. Supporting Evidence: PMID:15843410 Here, we show that the cooperative function of Pax3 and Zic1 determines the neural crest fate in the amphibian ectoderm. PMID:15843410 Misexpression of both Pax3 and Zic1 together efficiently induces ectopic neural crest differentiation in the ventral ectoderm, whereas overexpression of either one of them only expands the expression of neural crest markers within the dorsolateral ectoderm. PMID:15843410 Loss-of-function studies in vivo and in the animal cap show that co-presence of Pax3 and Zic1 is essential for the initiation of neural crest differentiation. PMID:24360906 We demonstrated that the neural border specifiers Pax3 and Zic1 are direct upstream regulators of neural crest specifiers Snail1/2, Foxd3, Twist1, and Tfap2b.
GO:0014034 neural crest cell fate commitment	IMP PMID:15843410 Neural crest determination by co-activation of Pax3 and Zic1...	ACCEPT	Summary: Pax3 and Zic1 together determine neural crest fate: their co-expression induces ectopic crest in ventral ectoderm and drives full crest determination, migration and differentiation; Zic1 directly activates the crest specifier snail1, and with Pax3 it activates snail2, foxd3, twist1, tfap2b and sox8. Reason: Core function: Zic1 knockdown blocks crest initiation and rescue restores it (full text). Same reasoning as the IGI row. Supporting Evidence: PMID:15843410 Loss-of-function studies in vivo and in the animal cap show that co-presence of Pax3 and Zic1 is essential for the initiation of neural crest differentiation. PMID:24360906 these results indicate that Zic1 is essential for snail1 induction at the neural border PMID:23509273 Thus, Pax3 and Zic1 cooperate and execute a transcriptional switch sufficient to activate full multipotent neural crest development and differentiation. file:XENLA/zic1/zic1-deep-research-falcon.md Pax3 could not substitute for depleted Zic1 in that assay, supporting the need for both activities rather than treating them as interchangeable factors.
GO:0014034 neural crest cell fate commitment	IMP PMID:9739105 Xenopus Zic family and its role in neural and neural crest d...	ACCEPT	Summary: Zic1 overexpression induces neural crest markers and crest-derived tissue. Reason: Gain-of-function only, which alone would be read as over-annotation (project rule, 2026-10-09); accepted because the Sato 2005 loss-of-function rows (PMID:15843410) independently establish crest fate commitment for Zic1. Supporting Evidence: PMID:9739105 We observed enhanced neural and neural crest-derived tissue formation in the Zic1 or Zic2 overexpressed embryos and neural and neural crest marker induction in the Zic1 or Zic2 overexpressed animal cap explants. PMID:9739105 the Xenopus Zic family may act cooperatively in the initial phase of neural and neural crest development.
GO:0021904 dorsal/ventral neural tube patterning	IMP PMID:9655809 Opl: a zinc finger protein that regulates neural determinati...	KEEP AS NON CORE	Summary: Activated Opl induces dorsal neural tube markers, and zic1 expression is restricted to the dorsal neural tube from neurula stages. Reason: A real later role in dorsal neural tube patterning, conserved for Zic genes, but separate from the core border specifier role. Supporting Evidence: PMID:9655809 the activated form of opl is able to induce neural crest and dorsal neural tube markers both in animal caps and whole embryos. PMID:9655809 At the onset of gastrulation, opl is expressed throughout the presumptive neural plate, indicating that neural determination has begun at this stage while, by neurula, opl expression is restricted to the dorsal neural tube and neural crest.
GO:0022008 neurogenesis	IMP PMID:9435279 Xenopus Zic-related-1 and Sox-2, two factors induced by chor...	KEEP AS NON CORE	Summary: Zic-r1 (Zic1) activates the proneural gene ngnr-1 and initiates neural and neuronal differentiation in animal caps and in vivo. Reason: Reflects the early neural-induction role of Zic1 (with Zic3). Real, but upstream of and broader than the core border function; neurogenesis is a broad term for this early neural fate role. Supporting Evidence: PMID:9435279 Zic-r1 mRNA injection activates the proneural gene Xngnr-1, and initiates neural and neuronal differentiation in isolated animal caps and in vivo. PMID:19805078 Finally, Zic1 and Zic3 are required together for definitive neural fate acquisition, both in ectopic and endogenous situations.
GO:0030177 positive regulation of Wnt signaling pathway	IGI PMID:16892174 The zic1 gene is an activator of Wnt signaling.	KEEP AS NON CORE	Summary: Zic1 induces transcription of wnt1, wnt4 and wnt8b, and Wnt signaling is required for Zic1/Noggin induction of the midbrain-hindbrain marker en-2. Reason: Zic1 increases Wnt signaling by activating Wnt ligand genes, so the term is defensible (mechanism: transcription of ligands, not a pathway component). This is a neural plate regionalization output, non-core to the border specifier role. Wnt is also needed alongside Pax3+Zic1 for crest induction. Supporting Evidence: PMID:16892174 Zic1 induces expression of several wnt genes, including wnt1, wnt4 and wnt8b. PMID:16892174 we demonstrate that an active Wnt pathway is required for activation of en-2 expression by zic1. PMID:16892174 While Zic1 does not act as a neural inducer, it synergizes with the neural inducing factor Noggin to activate expression of posterior neural genes, including the midbrain/hindbrain boundary marker engrailed-2.
GO:0042307 positive regulation of protein import into nucleus	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Transferred from mouse Zic1, which co-translocates Gli proteins to the nucleus when both are overexpressed in cultured cells. Reason: The mouse evidence is an overexpression co-translocation of a binding partner, not regulation of the nuclear import machinery. No frog evidence; the frog Zic1-Gli1-Zyxin interaction work concerns Gli nuclear retention by protein complex formation. Not a function to propagate as a process. Supporting Evidence: PMID:11238441 Moreover, Gli proteins were translocated to cell nuclei by coexpressed Zic proteins, and both proteins regulated each other's transcriptional activity.
GO:0045893 positive regulation of DNA-templated transcription	IDA PMID:9655809 Opl: a zinc finger protein that regulates neural determinati...	ACCEPT	Summary: Zic1 activates transcription of its targets (Opl is a transcriptional activator). The original paper shows transactivation by Opl. Reason: Correct; Pol II-specific child GO:0045944 also present. Supporting Evidence: PMID:9655809 opl encodes a transcriptional activator, with a carboxy terminal regulatory domain, which when removed increases opl activity.
GO:0045893 positive regulation of DNA-templated transcription	IMP PMID:16871635 The Xfeb gene is directly upregulated by Zic1 during early n...	ACCEPT	Summary: Zic1 directly upregulates Xfeb. Reason: Correct; Pol II-specific child GO:0045944 also present. Supporting Evidence: PMID:16871635 We have identified a new direct downstream target gene of Zic1 that we have named Xfeb.
GO:0045944 positive regulation of transcription by RNA polymerase II	IDA PMID:9655809 Opl: a zinc finger protein that regulates neural determinati...	ACCEPT	Summary: Zic1 activates transcription of its targets (Opl is a transcriptional activator). Reason: Core process for a DNA-binding activator; Zic1 directly activates snail1 and other Pol II genes. Supporting Evidence: PMID:9655809 opl encodes a transcriptional activator, with a carboxy terminal regulatory domain, which when removed increases opl activity. PMID:24360906 Firstly, the main known neural crest specifiers, snail1, snail2 and twist1, were highly and reproducibly activated either by Pax3 (snail2, twist1) or by Zic1 (snail1) in the presence of cycloheximide.
GO:0045944 positive regulation of transcription by RNA polymerase II	IMP PMID:16871635 The Xfeb gene is directly upregulated by Zic1 during early n...	ACCEPT	Summary: Zic1 directly upregulates Xfeb transcription. Reason: Direct target activation. Supporting Evidence: PMID:16871635 We have identified a new direct downstream target gene of Zic1 that we have named Xfeb.
GO:0045944 positive regulation of transcription by RNA polymerase II	IMP PMID:16892174 The zic1 gene is an activator of Wnt signaling.	ACCEPT	Summary: Zic1 activates transcription of wnt1, wnt4, wnt8b and en-2. Reason: Transcriptional activation of target genes; may be partly indirect (via Wnt1) for en-2, but Zic1 induction of wnt genes supports the term. Supporting Evidence: PMID:16892174 Zic1 induces expression of several wnt genes, including wnt1, wnt4 and wnt8b.
GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific	IDA PMID:24360906 Pax3 and Zic1 trigger the early neural crest gene regulatory...	NEW	Summary: Frog Zic1 is a sequence-specific transcriptional activator: it binds a conserved snail1 upstream element (EMSA, mutant-oligonucleotide control) and activates snail1 as an immediate-early (cycloheximide-resistant) target; Opl was characterized as a transcriptional activator. Reason: Existing MF rows stop at generic Pol II DNA-binding transcription factor activity. Direct binding, translation-independent activation and transactivation support the activator child term, matching pax3-a. No frog evidence of repression, so no repressor term. Mouse Zic1 carries GO:0001228 by IDA (PMID:11053430). Supporting Evidence: PMID:24360906 Similarly, we showed that Zic1 binds to snail1 putative oligonucleotide but not to the snail1 oligonucleotide mutated on the putative binding site (Figure 4E and not shown). PMID:24360906 Firstly, the main known neural crest specifiers, snail1, snail2 and twist1, were highly and reproducibly activated either by Pax3 (snail2, twist1) or by Zic1 (snail1) in the presence of cycloheximide. PMID:9655809 opl encodes a transcriptional activator, with a carboxy terminal regulatory domain, which when removed increases opl activity.
GO:0060788 ectodermal placode formation	IMP PMID:17409353 The activity of Pax3 and Zic1 regulates three distinct cell ...	NEW	Summary: Acting without high Pax3, Zic1 is necessary and sufficient for preplacodal ectoderm fate at the anterior neural plate border: Zic1GR induces Six1 and Eya1 in explants, and Zic1 knockdown removes Six1 and preplacodal Sox2. Reason: Participation: Zic1 is the transcription factor that activates the preplacodal specifiers (six1, eya1), so it does work in placode formation rather than being merely required. Comparator check (QuickGO, experimental, exact term): other preplacodal border/competence factors carry GO:0060788 (zebrafish tfap2a, tfap2c, gata3, foxi1; X. laevis tbx1-a). GO has no preplacodal ectoderm term; GO:0060788 is the closest existing process. Non-core relative to crest, but part of the border specifier function. Supporting Evidence: PMID:17409353 Using gain of function and knockdown approaches in whole embryos and animal explants, we demonstrate that Pax3 and Zic1 are necessary and sufficient to promote hatching gland and preplacodal fates, respectively, whereas their combined activity is essential to specify the neural crest. PMID:17409353 In these explants, a strong activation of the PE markers Six1 ( Figure 7 A) and Eya1 (data not shown) was observed in response to Zic1GR injection PMID:17409353 We also found that Six1 expression (75%; n = 74) and the preplacodal expression domain of Sox2 (89%; n = 59) were strongly inhibited in morpholino-injected embryos ( Figure 7 B).

Gene Description

Proposed New Ontology Terms

neural plate border formation

Existing Annotations Review

Core Functions

Neural plate border specifier. Induced in the lateral and anterior neural plate border during gastrulation, before the crest specifiers, Zic1 acts as a DNA-binding transcriptional activator that, with Pax3, establishes the border territory from which neural crest arises.

Preplacodal ectoderm fate at the anterior neural plate border. Acting without high Pax3, Zic1 activates six1 and eya1 and is required for preplacodal ectoderm.

Early neural plate gene. Directly induced by BMP inhibition, Zic1 (with Zic3) is required for definitive neural fate and patterns the neural plate through targets such as Xfeb.

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Notes

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