Affinage

ZIC1

Zinc finger protein ZIC 1 · UniProt Q15915

Length
447 aa
Mass
48.3 kDa
Annotated
2026-04-28
100 papers in source corpus 30 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ZIC1 is a zinc finger transcription factor that functions as a central regulator of neural progenitor maintenance, neural crest specification, and neuronal subtype differentiation across multiple regions of the developing nervous system. ZIC1 binds GLI-like DNA sequences and enhancer elements containing CTGCTG-core motifs, directly activating targets such as apolipoprotein E and Myf5 while repressing proneural genes like Math1 to maintain progenitor pools in the cerebellum, spinal cord, and forebrain (PMID:11053430, PMID:12642498, PMID:25849986, PMID:9412507, PMID:11944941). Beyond direct DNA binding, ZIC1 acts as a transcriptional co-factor by physically interacting with Gli proteins to modulate Hedgehog signaling, with Pax3 to cooperatively specify neural crest fate and activate neural crest specifier genes (Snail1/2, Foxd3, Twist1), and with β-catenin/TCF4 to inhibit Wnt target gene expression; its nuclear import is regulated by I-mfa binding and CRM1-dependent shuttling (PMID:11238441, PMID:15843410, PMID:24360906, PMID:31909528, PMID:15207726). Gain-of-function mutations in ZIC1 that escape nonsense-mediated decay cause coronal craniosynostosis through enhanced activation of the target gene engrailed-2 (PMID:26340333).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1994 Medium

    Establishing that ZIC1 is a nuclear zinc finger protein capable of binding GLI-consensus DNA sequences resolved its identity as a candidate transcription factor in cerebellar granule cells.

    Evidence Bacterially expressed Zic protein EMSA with GLI-binding sequence; immunohistochemistry in mouse cerebellum

    PMID:7931345

    Open questions at the time
    • Binding affinity relative to GLI not quantified
    • No functional transcriptional assay performed
    • In vivo relevance of GLI-site binding unknown
  2. 1998 High

    Knockout and gain-of-function studies in mouse and Xenopus established ZIC1 as a functional regulator of neural progenitor proliferation downstream of BMP inhibition and upstream of proneural genes, placing it within the neural induction hierarchy.

    Evidence Zic1 knockout mice with BrdU labeling of cerebellar EGL; Xenopus mRNA injection activating Xngnr-1 in animal caps

    PMID:9412507 PMID:9435279

    Open questions at the time
    • Direct transcriptional targets not identified
    • Whether proliferation defect is cell-autonomous not resolved
  3. 2000 High

    Systematic binding-site selection and reporter assays defined ZIC1's DNA-binding specificity as overlapping but distinct from GLI, and identified the APOE promoter as a direct transcriptional target, establishing ZIC1 as a bona fide sequence-specific transcriptional activator.

    Evidence CASTing/EMSA with mutagenesis; yeast one-hybrid with APOE promoter; co-transfection reporter assays in glioblastoma cells

    PMID:11038359 PMID:11053430

    Open questions at the time
    • Genome-wide target spectrum unknown
    • In vivo relevance of APOE regulation not demonstrated
  4. 2001 High

    Demonstration that ZIC1 physically interacts with Gli proteins via zinc finger domains and promotes their nuclear translocation revealed a co-factor mechanism through which ZIC1 modulates Hedgehog pathway output.

    Evidence Co-immunoprecipitation; subcellular localization assays; transcriptional reporter assays with co-transfection

    PMID:11238441

    Open questions at the time
    • Stoichiometry and structural basis of Zic-Gli interaction unknown
    • In vivo Hedgehog pathway modulation not tested genetically
  5. 2002 High

    Misexpression and compound mutant studies showed that ZIC1 actively inhibits neuronal differentiation to expand dorsal progenitor pools in the spinal cord and cerebellum, with Notch pathway upregulation and cell cycle regulator changes as downstream effectors.

    Evidence Chick electroporation; transgenic mouse overexpression; Zic1 KO; compound Zic1/Zic2 mutant mice with cyclin D1/p27 analysis

    PMID:11756505 PMID:11944941

    Open questions at the time
    • Whether Notch upregulation is a direct transcriptional target of ZIC1 or indirect
    • Mechanistic relationship between ZIC1 and cell cycle regulators not established
  6. 2003 High

    Identification of the Math1 enhancer as a direct ZIC1-bound repression target explained how ZIC1 counteracts neuronal differentiation at the transcriptional level by blocking proneural gene autoregulation.

    Evidence EMSA demonstrating direct Zic1 binding to Math1 enhancer; chick neural tube electroporation with Math1 enhancer-lacZ reporter

    PMID:12642498

    Open questions at the time
    • Whether ZIC1 recruits corepressors to the Math1 enhancer not determined
    • Genome-wide repressive targets not mapped
  7. 2004 High

    Discovery that I-mfa binds the ZIC1 N-terminal domain and blocks its nuclear import established a post-translational regulatory mechanism controlling ZIC1 subcellular localization and transcriptional activity.

    Evidence Co-IP; nuclear localization assays; reporter assays; domain mapping showing specificity for Zic1-3 but not Zic4/5

    PMID:15207726

    Open questions at the time
    • Physiological context where I-mfa regulates ZIC1 in vivo not demonstrated
    • Whether I-mfa sequesters ZIC1 in cytoplasm or promotes degradation unclear
  8. 2005 High

    Combinatorial gain- and loss-of-function experiments revealed that Pax3 and Zic1 together are necessary and sufficient for neural crest specification, with Zic1 alone promoting preplacodal fate, establishing a combinatorial transcription factor code at the neural plate border.

    Evidence mRNA co-injection and morpholino knockdown in Xenopus; animal cap assays showing fate switching

    PMID:15843410 PMID:17409353

    Open questions at the time
    • Whether Pax3 and Zic1 form a physical complex on chromatin not established
    • Enhancer-level logic of combinatorial binding unknown
  9. 2007 High

    Compound Zic1/Zic3 mutant analysis extended ZIC1's progenitor maintenance role to the medial forebrain (hippocampus, septum) and meninges, showing that Zic1/Zic3 loss increases premature cell cycle exit and disrupts pial basement membrane assembly.

    Evidence Compound mutant mice; BrdU/Ki67 cell cycle analysis; in utero electroporation; immunohistochemistry for basement membrane markers

    PMID:17507568 PMID:18448648

    Open questions at the time
    • Direct transcriptional targets mediating meningeal and basement membrane phenotypes unknown
    • Whether meningeal role is separable from brain patterning role unclear
  10. 2011 High

    Genetic epistasis with Shh pathway components demonstrated that ZIC1's role in cerebellar granule cell proliferation has both Shh-dependent (via Gli1/Ptch1/Mycn regulation) and Shh-independent (folial patterning) components, refining the Zic-Hedgehog interaction model; simultaneously, Zic1 was shown to synergize with Pax3 and Gli2 to activate the Myf5 epaxial enhancer during myogenesis.

    Evidence Compound Zic1/Zic4 and Shh mutant mice; Zic2-Gli2 co-IP; ChIP at Myf5 locus; reporter assays with domain mutagenesis

    PMID:21211521 PMID:21307096 PMID:24036067

    Open questions at the time
    • Whether ZIC1 directly binds Shh pathway regulatory elements in vivo not shown by ChIP
    • Structural basis of Pax3-Zic1-Gli2 synergy at enhancers unresolved
  11. 2013 High

    Transcriptomic identification of immediate Pax3/Zic1 targets (Snail1/2, Foxd3, Twist1, Tfap2b, Axin2, Cyp26c1) using translation blockade, combined with demonstration that Pax3/Zic1 co-expression drives full neural crest commitment including migration and multi-lineage differentiation, completed the picture of ZIC1 as a master neural crest specification factor.

    Evidence Cycloheximide-treated Xenopus animal caps with microarray; in vivo transplantation of Pax3/Zic1-induced cells in Xenopus and chick

    PMID:23509273 PMID:24360906

    Open questions at the time
    • ChIP-seq for direct Pax3/Zic1 co-occupancy at neural crest gene enhancers not performed
    • Epigenetic remodeling events during neural crest commitment not characterized
  12. 2015 High

    Genome-wide chromatin profiling in cerebellar granule neurons revealed ZIC1/ZIC2 binding at enhancers marked by CTGCTG-core motifs and H3K27ac, demonstrating that ZIC1 coordinates mature neuronal gene expression programs through enhancer regulation; separately, ZIC1 was shown to promote placode fate non-cell-autonomously by inducing RALDH2/LPGDS-dependent retinoic acid signaling; and ZIC1 gain-of-function mutations were linked to coronal craniosynostosis.

    Evidence ChIP-seq/DNase-seq/RNA-seq in mouse CGNs; Xenopus Zic1 gain-of-function with RALDH2/LPGDS morpholino epistasis; patient mutation NMD assay and Xenopus engrailed-2 functional assay

    PMID:25849986 PMID:26101153 PMID:26340333

    Open questions at the time
    • 3D chromatin architecture at ZIC1-bound enhancers not characterized
    • Whether craniosynostosis mutations alter ZIC1 DNA-binding specificity or partner interactions unknown
    • Mechanism linking RA production to placode specification at single-cell resolution unresolved
  13. 2020 Medium

    Demonstration that ZIC1 physically disrupts the β-catenin/TCF4 complex to suppress Wnt target genes (c-Myc, Cyclin D1) established a direct protein-protein mechanism for ZIC1's antagonism of canonical Wnt signaling, relevant in gastric cancer suppression.

    Evidence Co-immunoprecipitation; LEF reporter assay; invasion assay; mouse xenograft

    PMID:31909528

    Open questions at the time
    • Whether β-catenin/TCF4 disruption occurs on chromatin or in nucleoplasm unclear
    • Structural basis of ZIC1-β-catenin interaction not determined
    • Single-lab finding in cancer context; physiological developmental relevance of this mechanism not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the genome-wide enhancer logic of ZIC1 co-occupancy with Pax3 and Gli proteins, the structural basis of ZIC1's multi-partner interactions, and how ZIC1's dual roles as a transcriptional activator and repressor are determined at specific genomic loci.
  • No crystal or cryo-EM structure of ZIC1 or ZIC1-partner complexes available
  • Genome-wide co-occupancy maps for ZIC1 with Pax3/Gli/TCF not generated
  • Mechanism selecting activation versus repression at individual target loci unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0003677 DNA binding 5 GO:0098772 molecular function regulator activity 3
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 1
Pathway
R-HSA-1266738 Developmental Biology 9 R-HSA-162582 Signal Transduction 6 R-HSA-74160 Gene expression (Transcription) 6
Partners
CTNNB1GLI1GLI2GLI3MDFIPAX3TCF4ZIC2

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 ZIC1 (zic) protein contains zinc finger domains that bind to the GLI-binding DNA sequence, and localizes to the nucleus of cerebellar granule cells and their precursors. Bacterially expressed Zic protein binding assay (EMSA with GLI-binding sequence); immunohistochemical localization Journal of neurochemistry Medium 7931345
1998 Mouse Zic1 knockout causes cerebellar hypoplasia with missing anterior lobe lobule, associated with reduced cell proliferation in the external germinal layer (EGL), establishing Zic1 as a regulator of granule cell progenitor proliferation in cerebellar development. Homozygous Zic1 knockout mice; BrdU labeling of proliferating cells in EGL The Journal of neuroscience High 9412507
1998 Xenopus Zic-related-1 (Zic-r1/Zic1 ortholog) acts downstream of the neural inducer Chordin and upstream of the proneural gene Xngnr-1 to initiate neural and neuronal differentiation; mRNA injection activates Xngnr-1 and initiates neural differentiation in animal caps. mRNA injection in Xenopus embryos and animal cap assay; differential screen for Chordin/BMP-4-regulated genes Development High 9435279
2000 Zic1, Zic2, and Zic3 proteins bind a DNA sequence nearly identical to the GLI binding sequence (established by EMSA-based target selection and mutational analysis), but with lower affinity than GLI; they activate transcription from a wide range of promoters irrespective of GLI binding sequence; when co-transfected with GLI proteins, Zic proteins enhance or suppress GLI-mediated transactivation in a cell-type-dependent manner. EMSA-based target selection (CASTing), mutational analysis, reporter/transactivation assays, co-transfection with GLI proteins The Journal of biological chemistry High 11053430
2000 Zic1 and Zic2 bind to specific sequences in the apolipoprotein E (APOE) gene promoter (at regions -136/-125, -65/-54, and -185/-174) and transactivate APOE expression in glioblastoma cells. Yeast one-hybrid screen of human brain cDNA library with APOE promoter bait; EMSA confirmation; co-transfection reporter assays; ectopic expression measuring endogenous APOE The Journal of biological chemistry High 11038359
2001 Zic and Gli proteins physically interact through their zinc finger domains; Gli proteins are translocated to cell nuclei by coexpressed Zic proteins; Zic and Gli proteins mutually regulate each other's transcriptional activity, suggesting Zic proteins modulate the hedgehog signaling pathway. Co-immunoprecipitation; subcellular localization assays; transcriptional reporter assays with co-transfection The Journal of biological chemistry High 11238441
2002 Zic1 inhibits neuronal differentiation and promotes expansion of dorsal neural progenitors in the spinal cord; misexpression of Zic1 on the ventral side of chick spinal cord inhibits neuronal differentiation; Notch1 is upregulated in Zic1-overexpressing spinal cords, suggesting Notch-mediated inhibition of neuronal differentiation acts downstream of Zic1. Chick in ovo electroporation (misexpression); transgenic mouse overexpression; Zic1 knockout mice; molecular marker analysis Developmental biology High 11944941
2002 Zic1 and Zic2 cooperatively control cerebellar development by regulating neuronal differentiation; compound Zic1(+/-)Zic2(+/kd) mice show cerebellar foliation abnormalities with reduced cyclin D1 and increased p27/p16 expression in the anterior EGL, and enhanced Wnt7a expression. Genetic compound mutant mouse analysis; molecular marker expression analysis The Journal of neuroscience High 11756505
2003 Zic1 binds a conserved site within the Math1 enhancer and represses Math1/Cath1 transcription; Zic1-mediated repression blocks the autoregulatory activity of Math1 itself, counteracting neuronal differentiation in the dorsal spinal cord. EMSA (Zic1 binding to Math1 enhancer); chick neural tube electroporation with Math1 enhancer-lacZ reporter; in ovo misexpression of Zic1 Development High 12642498
2003 The intracellular domain of teneurin-2 represses Zic1-mediated transcription from the apolipoprotein E promoter; teneurin-2 intracellular domain colocalizes with PML protein in nuclear bodies; release of the intracellular domain can be stimulated by homophilic interaction of teneurin-2 extracellular domain. Transcriptional reporter assays; nuclear colocalization by immunofluorescence; proteasome inhibitor stabilization experiments Journal of cell science Medium 12783990
2004 I-mfa (inhibitor of MyoD family) physically interacts with the amino-terminal domain of Zic proteins (Zic1-3) and inhibits their nuclear import, thereby suppressing Zic-mediated transcriptional activation; this interaction does not occur with Zic4/Zic5, whose N-terminal regions differ. Co-immunoprecipitation; nuclear localization assays; transcriptional reporter assays; domain mapping Biochemical and biophysical research communications High 15207726
2005 Cooperative function of Pax3 and Zic1 determines neural crest fate in Xenopus ectoderm; co-expression of both factors efficiently induces ectopic neural crest in ventral ectoderm; the induction requires Wnt signaling; loss-of-function of both is required to block neural crest initiation. mRNA co-injection (gain-of-function); morpholino knockdown (loss-of-function); animal cap assay; in vivo ectopic induction Development High 15843410
2006 Zic1 acts as an upstream activator of Wnt signaling in Xenopus; Zic1 induces expression of wnt1, wnt4, and wnt8b genes; activation of engrailed-2 by Zic1 requires an active Wnt pathway (blocked by Wnt inhibitors); this parallels the Drosophila opa-wingless-engrailed regulatory relationship. mRNA injection; Wnt signaling inhibitor treatment; RT-PCR for Wnt target genes; reporter assays The International journal of developmental biology Medium 16892174
2007 Pax3 and Zic1 have distinct individual activities at the neural plate border: Pax3 alone promotes hatching gland fate, Zic1 alone promotes preplacodal fate, and their combined activity is necessary and sufficient to specify neural crest; manipulating levels of Pax3 and Zic1 shifts cell fate among these three lineages. mRNA injection (gain-of-function); morpholino knockdown; animal cap assay in Xenopus Molecular biology of the cell High 17409353
2007 Zic1 and Zic3 are required for medial forebrain development; compound Zic1/Zic3 mutant mice show hippocampal, septal, and olfactory bulb hypoplasia associated with increased cell cycle exit rate in the septa; Zic3 misexpression in cortical ventricular layer inhibits neuronal differentiation, establishing both genes as maintainers of neural precursor undifferentiated state. Compound mutant mouse analysis; cell cycle analysis (BrdU/Ki67); in utero electroporation misexpression The Journal of neuroscience High 17507568
2008 Zic1 and Zic3 are expressed in meningeal progenitor cells; Zic1/Zic3 double-mutant mice show reduced meningeal cell proliferation, thinned and disrupted pial basement membrane, and cortical lamination defects resembling cobblestone lissencephaly; Zic genes regulate meningeal cell proliferation and pial basement membrane assembly. Compound mutant mouse analysis; immunohistochemistry; BrdU cell proliferation assay; marker expression The Journal of neuroscience High 18448648
2009 Zebrafish Zic1 knockdown causes midline defects and partial cyclopia by attenuating Nodal and Hedgehog signaling in the anterior ventral diencephalon; Zic1 is also required for maintaining forebrain expression of the RA-degrading enzyme cyp26a1, and its loss leads to increased RA levels, ventralization of the optic vesicle, and downregulation of dorsal BMP signaling. Morpholino knockdown in zebrafish; in situ hybridization for pathway target genes; signaling pathway analysis Genes & development High 19528322
2010 Zic1 is expressed in osteocytes (MLO-Y4 cells) in both cytosol and nucleus; prolonged oscillatory fluid flow (shear stress) induces nuclear translocation of Zic1 in osteocytes but not in osteoblast-like cells; Zic1 gene silencing abolishes shear stress-induced TCF/LEF transcriptional activity, implicating Zic1 in mechanosensory Wnt signaling in osteocytes. Immunolocalization; oscillatory fluid flow experiment; siRNA knockdown; TCF/LEF reporter assay FASEB journal Medium 20354137
2011 Zic1 and Zic4 have both Shh-dependent and Shh-independent roles in cerebellar development; Zic1/Zic4 mutants show decreased granule cell progenitor proliferation with downregulated Shh-downstream genes Ptch1, Gli1, and Mycn despite normal Shh production; folial patterning defects are Shh-independent. Compound Zic1/Zic4 mutant mice; genetic interaction with Shh heterozygotes; in situ hybridization for Shh pathway targets; conditional Smo/Gli2 knockouts as controls Development High 21307096
2011 Zic1 and Zic2 activate the Myf5 epaxial somite enhancer in a Gli-dependent manner; Zic2 co-immunoprecipitates with Gli2, forming complexes that promote Myf5 expression; Myf5 expression is deficient in Zic2 mutant embryos in newly forming somites; Zic1 activates endogenous Myf5 in 10T1/2 cells and presomitic mesoderm explants. Co-IP (Zic2-Gli2); transcriptional reporter assays; in vitro and in vivo Myf5 expression assays; Zic2 mutant mouse analysis Developmental biology High 21211521
2013 Pax3 and Zic1 directly activate multiple neural crest specifier genes (Snail1/2, Foxd3, Twist1, Tfap2b) as first-tier transcriptional targets; they also induce key pathway regulators of Wnt (Axin2) and retinoic acid (Cyp26c1) signaling; identified by combining gain-of-function with protein translation blockade (cycloheximide) and transcriptome microarray. Microarray transcriptomics combined with Pax3/Zic1 gain-of-function and translation blockade in Xenopus; morpholino validation Developmental biology High 24360906
2013 Pax3 and Zic1 co-activation is sufficient to trigger full neural crest commitment including migration and differentiation into multiple derivatives (melanocytes, neurons, glia, cartilage) in Xenopus and chicken; co-activated cells can migrate to and integrate into craniofacial target territories after transplantation. Co-injection of Pax3 and Zic1 mRNA; ectopic induction assays in multiple embryonic contexts; in vitro differentiation; in vivo transplantation PNAS High 23509273
2013 Pax3 synergizes with both Gli2 and Zic1 to transactivate the Myf5 epaxial somite enhancer; this synergy requires conserved functional domains and a homeodomain motif in the Myf5 promoter plus the Gli motif in the enhancer; overexpression of Zic1 and Pax3 results in enrichment of these factors at the endogenous Myf5 locus and induction of Myf5 expression. Reporter (transactivation) assays; ChIP at endogenous Myf5 locus; domain deletion mutagenesis; ectopic overexpression in 10T1/2 cells Developmental biology High 24036067
2015 ZIC1 gain-of-function mutations (nonsense and missense in exon 3) that escape nonsense-mediated decay are associated with coronal craniosynostosis; both mutation types lead to altered and/or enhanced expression of target gene engrailed-2 in Xenopus embryo assay; Zic1 is expressed at E11.5-12.5 in a region overlapping the supraorbital regulatory center patterning the coronal suture. Cell line NMD assay; Xenopus target gene (engrailed-2) reporter/expression assay; mouse embryo in situ hybridization for Zic1 expression domain American journal of human genetics Medium 26340333
2015 Zic1 promotes cranial placode progenitor specification non-cell autonomously by inducing RALDH2 and LPGDS, which respectively regulate synthesis and transport of retinoic acid (RA); RA signaling in turn activates a placode developmental program in neighboring cells. Xenopus gain-of-function (Zic1 mRNA injection); gene expression screen; morpholino knockdown of RALDH2 and LPGDS; RA pathway manipulation Nature communications High 26101153
2015 Zic1 and Zic2 are required in cerebellar granule neurons (CGNs) for coordinating mature neuronal gene expression patterns; Zic binding is enriched at chromatin regions containing CTGCTG-core motifs at enhancers; Zic1/Zic2 knockdown disrupts enhancer-associated gene expression programs during CGN differentiation. DNase-seq; H3K27ac ChIP-seq; Zic1/2 ChIP-seq; RNA-seq; CRISPR-mediated activation; knockdown in mouse CGNs Nature neuroscience High 25849986
2015 Brn2 directly regulates Zic1 expression; Zic1 is a downstream target in a hierarchical Brn2-Zic1 axis essential for specifying neural fate in retinoic-acid-treated embryonic stem cells; shRNA-mediated silencing of Zic1 prevents ESC differentiation into neuronal precursors. RNA-seq after Brn2 silencing; Brn2 ChIP-seq; shRNA knockdown of Zic1 with differentiation assay Journal of cell science Medium 25991548
2017 Zic1 and Zic2 promote calretinin-positive GABAergic interneuron fate while suppressing dopaminergic fate in the postnatal dorsal forebrain; this dopaminergic repressor function of Zic proteins is evolutionarily conserved in C. elegans. Lentiviral gain-of-function overexpression; gene expression analysis; in vivo mouse model; C. elegans genetic analysis The Journal of neuroscience Medium 28972122
2018 Zic proteins (including Zic1) undergo nucleocytoplasmic shuttling via importin- and CRM1-based mechanisms; degradation is mediated by the ubiquitin proteasome system; Zic proteins bind two types of DNA sequences (CTGCTG-core-type and GC-stretch-type); Zic1 interacts with multiple proteins including Gli1-3, Tcf1/Tcf4, Smad2/3, Oct4, Pax3, Cdx, SRF, and chromatin-remodeling factors NuRD and NURF. Review summarizing multiple experimental approaches including ChIP, co-IP, nuclear transport inhibitor assays, proteasome inhibitor assays Advances in experimental medicine and biology Medium 29442331
2020 Zic1 physically interacts with β-catenin/TCF4 and disrupts their complex formation without affecting β-catenin nuclear localization, thereby downregulating Wnt target genes (c-Myc, Cyclin D1) and suppressing gastric cancer cell invasion and EMT. Co-immunoprecipitation; LEF transcriptional reporter assay; cell invasion assay; mouse xenograft model; western blot FASEB journal Medium 31909528

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 Xenopus Zic-related-1 and Sox-2, two factors induced by chordin, have distinct activities in the initiation of neural induction. Development (Cambridge, England) 392 9435279
1997 The expression of the mouse Zic1, Zic2, and Zic3 gene suggests an essential role for Zic genes in body pattern formation. Developmental biology 280 9070329
2004 The role of Zic genes in neural development. Molecular and cellular neurosciences 224 15207846
1994 A novel zinc finger protein, zic, is involved in neurogenesis, especially in the cell lineage of cerebellar granule cells. Journal of neurochemistry 207 7931345
1998 Gli/Zic factors pattern the neural plate by defining domains of cell differentiation. Nature 192 9634234
2005 Neural crest determination by co-activation of Pax3 and Zic1 genes in Xenopus ectoderm. Development (Cambridge, England) 174 15843410
1996 The mouse zic gene family. Homologues of the Drosophila pair-rule gene odd-paired. The Journal of biological chemistry 171 8557628
1998 Mouse Zic1 is involved in cerebellar development. The Journal of neuroscience : the official journal of the Society for Neuroscience 159 9412507
2001 Physical and functional interactions between Zic and Gli proteins. The Journal of biological chemistry 158 11238441
2000 Molecular properties of Zic proteins as transcriptional regulators and their relationship to GLI proteins. The Journal of biological chemistry 152 11053430
2007 Evaluation and optimization of ZIC-HILIC-RP as an alternative MudPIT strategy. Journal of proteome research 146 17256977
2007 The activity of Pax3 and Zic1 regulates three distinct cell fates at the neural plate border. Molecular biology of the cell 146 17409353
1998 Xenopus Zic family and its role in neural and neural crest development. Mechanisms of development 145 9739105
2015 Regulation of chromatin accessibility and Zic binding at enhancers in the developing cerebellum. Nature neuroscience 131 25849986
1996 Predominant expression of human zic in cerebellar granule cell lineage and medulloblastoma. Cancer research 124 8542595
2007 Emerging roles for zic genes in early development. Developmental dynamics : an official publication of the American Association of Anatomists 123 17330889
2005 The ZIC gene family in development and disease. Clinical genetics 120 15733262
2002 Zic2 controls cerebellar development in cooperation with Zic1. The Journal of neuroscience : the official journal of the Society for Neuroscience 116 11756505
2002 Zic1 promotes the expansion of dorsal neural progenitors in spinal cord by inhibiting neuronal differentiation. Developmental biology 115 11944941
2011 Zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC and ZIC-cHILIC) provide high resolution separation and increase sensitivity in proteome analysis. Analytical chemistry 106 21443167
2009 BMP inhibition initiates neural induction via FGF signaling and Zic genes. Proceedings of the National Academy of Sciences of the United States of America 105 19805078
2013 Pax3 and Zic1 trigger the early neural crest gene regulatory network by the direct activation of multiple key neural crest specifiers. Developmental biology 101 24360906
2002 Multiple functions of a Zic-like gene in the differentiation of notochord, central nervous system and muscle in Ciona savignyi embryos. Development (Cambridge, England) 101 12015299
2007 Zic1 and Zic3 regulate medial forebrain development through expansion of neuronal progenitors. The Journal of neuroscience : the official journal of the Society for Neuroscience 95 17507568
2013 Pax3 and Zic1 drive induction and differentiation of multipotent, migratory, and functional neural crest in Xenopus embryos. Proceedings of the National Academy of Sciences of the United States of America 92 23509273
2011 Multiple developmental programs are altered by loss of Zic1 and Zic4 to cause Dandy-Walker malformation cerebellar pathogenesis. Development (Cambridge, England) 88 21307096
2000 A novel member of the Xenopus Zic family, Zic5, mediates neural crest development. Mechanisms of development 88 11091076
2012 BMP, Wnt and FGF signals are integrated through evolutionarily conserved enhancers to achieve robust expression of Pax3 and Zic genes at the zebrafish neural plate border. Development (Cambridge, England) 82 23034628
2003 The intracellular domain of teneurin-2 has a nuclear function and represses zic-1-mediated transcription. Journal of cell science 81 12783990
2014 Stem cell-dependent formation of a functional anterior regeneration pole in planarians requires Zic and Forkhead transcription factors. Developmental biology 80 24704339
2013 The ZIC gene family encodes multi-functional proteins essential for patterning and morphogenesis. Cellular and molecular life sciences : CMLS 79 23443491
2003 Zic1 represses Math1 expression via interactions with the Math1 enhancer and modulation of Math1 autoregulation. Development (Cambridge, England) 78 12642498
2014 zic-1 Expression in Planarian neoblasts after injury controls anterior pole regeneration. PLoS genetics 70 24992682
2011 Elucidation of glycoprotein structures by unspecific proteolysis and direct nanoESI mass spectrometric analysis of ZIC-HILIC-enriched glycopeptides. Journal of proteome research 69 21443200
2003 A genomewide survey of developmentally relevant genes in Ciona intestinalis. IV. Genes for HMG transcriptional regulators, bZip and GATA/Gli/Zic/Snail. Development genes and evolution 68 12743819
2006 A wide-range phylogenetic analysis of Zic proteins: implications for correlations between protein structure conservation and body plan complexity. Genomics 65 16574373
2008 Zic deficiency in the cortical marginal zone and meninges results in cortical lamination defects resembling those in type II lissencephaly. The Journal of neuroscience : the official journal of the Society for Neuroscience 63 18448648
1996 Identification and characterization of Zic4, a new member of the mouse Zic gene family. Gene 61 8682319
2015 Gain-of-Function Mutations in ZIC1 Are Associated with Coronal Craniosynostosis and Learning Disability. American journal of human genetics 55 26340333
2007 Zic1 and Zic4 regulate zebrafish roof plate specification and hindbrain ventricle morphogenesis. Developmental biology 55 18191121
2003 Protochordate Zic genes define primitive somite compartments and highlight molecular changes underlying neural crest evolution. Evolution & development 55 12622730
2011 ZIC1 is downregulated through promoter hypermethylation, and functions as a tumor suppressor gene in colorectal cancer. PloS one 54 21347233
2006 The zic1 gene is an activator of Wnt signaling. The International journal of developmental biology 51 16892174
2004 Hyzic, the Hydra homolog of the zic/odd-paired gene, is involved in the early specification of the sensory nematocytes. Development (Cambridge, England) 51 14681184
2002 HrzicN, a new Zic family gene of ascidians, plays essential roles in the neural tube and notochord development. Development (Cambridge, England) 51 12421701
1999 Zebrafish zic1 expression in brain and somites is affected by BMP and hedgehog signalling. Mechanisms of development 51 10415355
2000 Transcription factors Zic1 and Zic2 bind and transactivate the apolipoprotein E gene promoter. The Journal of biological chemistry 50 11038359
2013 Identification of Pax3 and Zic1 targets in the developing neural crest. Developmental biology 48 24360908
2009 ZIC1 is downregulated through promoter hypermethylation in gastric cancer. Biochemical and biophysical research communications 47 19135984
2014 ZIC1 is a putative tumor suppressor in thyroid cancer by modulating major signaling pathways and transcription factor FOXO3a. The Journal of clinical endocrinology and metabolism 46 24684457
2012 Zinc fingers of the cerebellum (Zic): transcription factors and co-factors. The international journal of biochemistry & cell biology 46 22964024
2010 Enhanced glyco-profiling by specific glycopeptide enrichment and complementary monolithic nano-LC (ZIC-HILIC/RP18e)/ESI-MS analysis. Journal of separation science 46 20222078
2006 Overlapping expression of FoxA and Zic confers responsiveness to FGF signaling to specify notochord in ascidian embryos. Developmental biology 46 16950241
2021 CircMTO1 suppresses hepatocellular carcinoma progression via the miR-541-5p/ZIC1 axis by regulating Wnt/β-catenin signaling pathway and epithelial-to-mesenchymal transition. Cell death & disease 45 34930906
2012 ZIC1 modulates cell-cycle distributions and cell migration through regulation of sonic hedgehog, PI(3)K and MAPK signaling pathways in gastric cancer. BMC cancer 45 22799764
2010 Expression of ZIC family genes in meningiomas and other brain tumors. BMC cancer 45 20199689
2009 Zic-associated holoprosencephaly: zebrafish Zic1 controls midline formation and forebrain patterning by regulating Nodal, Hedgehog, and retinoic acid signaling. Genes & development 43 19528322
2001 Behavioral abnormalities of Zic1 and Zic2 mutant mice: implications as models for human neurological disorders. Behavior genetics 43 11699604
2004 Myogenic repressor I-mfa interferes with the function of Zic family proteins. Biochemical and biophysical research communications 42 15207726
2010 ZIC1 overexpression is oncogenic in liposarcoma. Cancer research 41 20713527
2008 ZIC antibodies in paraneoplastic cerebellar degeneration and small cell lung cancer. Journal of neuroimmunology 41 18639938
2010 Expression and phylogenetic analysis of the zic gene family in the evolution and development of metazoans. EvoDevo 40 21054859
2020 Zygotic pioneer factor activity of Odd-paired/Zic is necessary for late function of the Drosophila segmentation network. eLife 38 32347792
2007 Direct activation by Ets and Zic is required for initial expression of the Brachyury gene in the ascidian notochord. Developmental biology 37 17459364
2017 Ultrathin Au nanowires assisted magnetic graphene-silica ZIC-HILIC composites for highly specific enrichment of N-linked glycopeptides. Analytica chimica acta 36 28433058
2015 Atypical Transcriptional Activation by TCF via a Zic Transcription Factor in C. elegans Neuronal Precursors. Developmental cell 36 26073017
2010 Zic1 transcription factor in bone: neural developmental protein regulates mechanotransduction in osteocytes. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 34 20354137
2017 Combined Detection of Plasma ZIC1, HOXD10 and RUNX3 Methylation is a Promising Strategy for Early Detection of Gastric Cancer and Precancerous Lesions. Journal of Cancer 32 28529617
2012 The medaka zic1/zic4 mutant provides molecular insights into teleost caudal fin evolution. Current biology : CB 32 22386310
2021 Performance of DNA methylation analysis of ASCL1, LHX8, ST6GALNAC5, GHSR, ZIC1 and SST for the triage of HPV-positive women: Results from a Dutch primary HPV-based screening cohort. International journal of cancer 31 34558659
2018 ZIC1 Function in Normal Cerebellar Development and Human Developmental Pathology. Advances in experimental medicine and biology 31 29442326
2021 ZIC-cHILIC-Based StageTip for Simultaneous Glycopeptide Enrichment and Fractionation toward Large-Scale N-Sialoglycoproteomics. Analytical chemistry 30 34780171
2020 Zic1 suppresses gastric cancer metastasis by regulating Wnt/β-catenin signaling and epithelial-mesenchymal transition. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 30 31909528
2015 Zic1 controls placode progenitor formation non-cell autonomously by regulating retinoic acid production and transport. Nature communications 30 26101153
2011 A role for Zic1 and Zic2 in Myf5 regulation and somite myogenesis. Developmental biology 30 21211521
2009 Xenopus Meis3 protein lies at a nexus downstream to Zic1 and Pax3 proteins, regulating multiple cell-fates during early nervous system development. Developmental biology 30 19944089
2003 Expression of ZIC genes in the development of the chick inner ear and nervous system. Developmental dynamics : an official publication of the American Association of Anatomists 30 12666207
2013 Pax3 synergizes with Gli2 and Zic1 in transactivating the Myf5 epaxial somite enhancer. Developmental biology 29 24036067
2013 ZIC1 is silenced and has tumor suppressor function in malignant pleural mesothelioma. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 29 24457242
2008 C2H2 zinc finger genes of the Gli, Zic, KLF, SP, Wilms' tumour, Huckebein, Snail, Ovo, Spalt, Odd, Blimp-1, Fez and related gene families from Branchiostoma floridae. Development genes and evolution 29 18795322
2011 Role of BMP, FGF, calcium signaling, and Zic proteins in vertebrate neuroectodermal differentiation. Neurochemical research 28 21336820
2010 Expression of the zic1, zic2, zic3, and zic4 genes in early chick embryos. BMC research notes 28 20553611
2016 Phosphatidylinositol glycan anchor biosynthesis, class X containing complex promotes cancer cell proliferation through suppression of EHD2 and ZIC1, putative tumor suppressors. International journal of oncology 27 27572108
2012 Comparison of ZIC-HILIC and graphitized carbon-based analytical approaches combined with exoglycosidase digestions for analysis of glycans from monoclonal antibodies. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 26 23217312
2007 The Zic family member, odd-paired, regulates the Drosophila BMP, decapentaplegic, during adult head development. Development (Cambridge, England) 26 17329368
2017 Zic-Proteins Are Repressors of Dopaminergic Forebrain Fate in Mice and C. elegans. The Journal of neuroscience : the official journal of the Society for Neuroscience 25 28972122
2015 A Brn2-Zic1 axis specifies the neuronal fate of retinoic-acid-treated embryonic stem cells. Journal of cell science 25 25991548
2007 Dicyema Pax6 and Zic: tool-kit genes in a highly simplified bilaterian. BMC evolutionary biology 25 17961212
2016 Gene regulatory networks in neural cell fate acquisition from genome-wide chromatin association of Geminin and Zic1. Scientific reports 24 27881878
2013 The MYC, TERT, and ZIC1 genes are common targets of viral integration and transcriptional deregulation in avian leukosis virus subgroup J-induced myeloid leukosis. Journal of virology 24 24371071
2011 The role of Zic family zinc finger transcription factors in the proliferation and differentiation of retinal progenitor cells. Biochemical and biophysical research communications 24 22024047
2018 ZIC1 acts a tumor suppressor in breast cancer by targeting survivin. International journal of oncology 23 29956756
2012 ZIC-cHILIC as a fractionation method for sensitive and powerful shotgun proteomics. Nature protocols 23 23099486
2010 Dandy-Walker malformation associated with heterozygous ZIC1 and ZIC4 deletion: Report of a new patient. American journal of medical genetics. Part A 23 21204220
2007 Visualization of two distinct classes of neurons by gad2 and zic1 promoter/enhancer elements in the dorsal hindbrain of developing zebrafish reveals neuronal connectivity related to the auditory and lateral line systems. Developmental dynamics : an official publication of the American Association of Anatomists 23 17279576
2018 Role of Zic Family Proteins in Transcriptional Regulation and Chromatin Remodeling. Advances in experimental medicine and biology 22 29442331
2004 Possible roles of zic1 and zic4, identified within the medaka Double anal fin (Da) locus, in dorsoventral patterning of the trunk-tail region (related to phenotypes of the Da mutant). Mechanisms of development 22 15210192
2016 Roles of ZIC family genes in human gastric cancer. International journal of molecular medicine 21 27177248
2006 The zic1 gene is expressed in chick somites but not in migratory neural crest. Gene expression patterns : GEP 21 16451832
2004 Molecular properties of Zic4 and Zic5 proteins: functional diversity within Zic family. Biochemical and biophysical research communications 21 15465018