Gene Symbol: Zic3
Description: zinc finger protein of the cerebellum 3
Alias: zinc finger protein ZIC 3, Zic family member 3 (odd-paired homolog, Drosophila)
Species: mouse
Products:     Zic3

Top Publications

  1. Gengyo Ando K, Kitayama H, Mukaida M, Ikawa Y. A murine neural-specific homolog corrects cholinergic defects in Caenorhabditis elegans unc-18 mutants. J Neurosci. 1996;16:6695-702 pubmed
    ..These data suggest that Munc-18-1 and C. elegans unc-18 may play positive roles in ACh release and that the molecular mechanism of neuronal regulated secretion has been partially conserved from nematodes to mammals. ..
  2. Ware S, Harutyunyan K, Belmont J. Heart defects in X-linked heterotaxy: evidence for a genetic interaction of Zic3 with the nodal signaling pathway. Dev Dyn. 2006;235:1631-7 pubmed
    ..Mutations in the zinc finger transcription factor ZIC3 cause X-linked heterotaxy, HTX1...
  3. Elms P, Scurry A, Davies J, Willoughby C, Hacker T, Bogani D, et al. Overlapping and distinct expression domains of Zic2 and Zic3 during mouse gastrulation. Gene Expr Patterns. 2004;4:505-11 pubmed
    ..with holoprosencephaly which is caused by a defect of ventral forebrain development and mutation of human and mouse Zic3 is associated with a X-linked heterotaxy syndrome that results from a failure of left-right axis formation...
  4. Aruga J, Yokota N, Hashimoto M, Furuichi T, Fukuda M, Mikoshiba K. A novel zinc finger protein, zic, is involved in neurogenesis, especially in the cell lineage of cerebellar granule cells. J Neurochem. 1994;63:1880-90 pubmed
    ..These findings suggest that zic is one of a number of nuclear factors involved in both differentiation in early development and maintenance of properties of the cerebellar granule cells. ..
  5. Inoue T, Ota M, Mikoshiba K, Aruga J. Zic2 and Zic3 synergistically control neurulation and segmentation of paraxial mesoderm in mouse embryo. Dev Biol. 2007;306:669-84 pubmed
    ..To uncover possible redundant roles, we characterized Zic2/Zic3 compound mutant mice...
  6. Quinn M, Haaning A, Ware S. Preaxial polydactyly caused by Gli3 haploinsufficiency is rescued by Zic3 loss of function in mice. Hum Mol Genet. 2012;21:1888-96 pubmed publisher
    ..A closely related Gli (glioma-associated oncogene homolog)-superfamily member, ZIC3, causes X-linked heterotaxy syndrome in humans but has not been investigated in limb development...
  7. Lim L, Hong F, Kunarso G, Stanton L. The pluripotency regulator Zic3 is a direct activator of the Nanog promoter in ESCs. Stem Cells. 2010;28:1961-9 pubmed publisher
    The transcription factor Zic3 is required for maintenance of ESC pluripotency...
  8. Hatayama M, Tomizawa T, Sakai Kato K, Bouvagnet P, Kose S, Imamoto N, et al. Functional and structural basis of the nuclear localization signal in the ZIC3 zinc finger domain. Hum Mol Genet. 2008;17:3459-73 pubmed publisher
    Disruptions in ZIC3 cause heterotaxy, a congenital anomaly of the left-right axis. ZIC3 encodes a nuclear protein with a zinc finger (ZF) domain that contains five tandem C2H2 ZF motifs...
  9. Sakai Kato K, Ishiguro A, Mikoshiba K, Aruga J, Utsunomiya Tate N. CD spectra show the relational style between Zic-, Gli-, Glis-zinc finger protein and DNA. Biochim Biophys Acta. 2008;1784:1011-9 pubmed publisher
    ..These results suggest that the alpha-helix structure is important for DNA binding and profoundly related to functional and structural diversity among the three families. ..

More Information


  1. Zhu L, Peng J, Harutyunyan K, Garcia M, Justice M, Belmont J. Craniofacial, skeletal, and cardiac defects associated with altered embryonic murine Zic3 expression following targeted insertion of a PGK-NEO cassette. Front Biosci. 2007;12:1680-90 pubmed
    Mutation in ZIC3 (OMIM #306955), a zinc finger transcription factor, causes heterotaxy (situs ambiguus) or isolated congenital heart defects in humans...
  2. Bogani D, Warr N, Elms P, Davies J, Tymowska Lalanne Z, Goldsworthy M, et al. New semidominant mutations that affect mouse development. Genesis. 2004;40:109-117 pubmed
    ..In one coat spotting mutant the homozygous condition is lethal before neural crest cell production commences. The mutated genes often function in processes additional to those alluded to by the heterozygous phenotype. ..
  3. Jiang Z, Zhu L, Hu L, Slesnick T, Pautler R, Justice M, et al. Zic3 is required in the extra-cardiac perinodal region of the lateral plate mesoderm for left-right patterning and heart development. Hum Mol Genet. 2013;22:879-89 pubmed publisher
    Mutations in ZIC3 cause human X-linked heterotaxy and isolated cardiovascular malformations. A mouse model with targeted deletion of Zic3 demonstrates an early role for Zic3 in gastrulation, CNS, cardiac and left-right axial development...
  4. Mizugishi K, Aruga J, Nakata K, Mikoshiba K. Molecular properties of Zic proteins as transcriptional regulators and their relationship to GLI proteins. J Biol Chem. 2001;276:2180-8 pubmed
    ..We first established an optimal binding sequence for Zic1, Zic2, and Zic3 proteins by electrophoretic mobility shift assay-based target selection and mutational analysis...
  5. Nagai T, Aruga J, Takada S, Gunther T, Spörle R, Schughart K, et al. The expression of the mouse Zic1, Zic2, and Zic3 gene suggests an essential role for Zic genes in body pattern formation. Dev Biol. 1997;182:299-313 pubmed
    We examined the expression of Zic1, Zic2, and Zic3 genes in the mouse embryo by means of in situ hybridization...
  6. Gebbia M, Ferrero G, Pilia G, Bassi M, Aylsworth A, Penman Splitt M, et al. X-linked situs abnormalities result from mutations in ZIC3. Nat Genet. 1997;17:305-8 pubmed
    ..From this chromosomal region we have positionally cloned ZIC3, a gene encoding a putative zinc-finger transcription factor...
  7. Klootwijk R, Franke B, Van der Zee C, de Boer R, Wilms W, Hol F, et al. A deletion encompassing Zic3 in bent tail, a mouse model for X-linked neural tube defects. Hum Mol Genet. 2000;9:1615-22 pubmed
    ..of several genes, combining data on ZIC:3 expression and function of ZIC: genes in the mouse shows that deletion of Zic3 alone is compatible with a major role of this gene in the congenital malformations of the Bent tail mouse...
  8. Ware S, Harutyunyan K, Belmont J. Zic3 is critical for early embryonic patterning during gastrulation. Dev Dyn. 2006;235:776-85 pubmed
    Mutations in the zinc finger transcription factor ZIC3 are associated with human left-right patterning abnormalities (X-linked heterotaxy, HTX1, MIM 306955), and mice null for Zic3 show a similar phenotype...
  9. Carrel T, Purandare S, Harrison W, Elder F, Fox T, Casey B, et al. The X-linked mouse mutation Bent tail is associated with a deletion of the Zic3 locus. Hum Mol Genet. 2000;9:1937-42 pubmed
    ..lt;170 kb submicroscopic deletion that includes the anonymous microsatellite marker DXMit208 as well as the entire Zic3 locus. Human mutations in ZIC3 are associated with left-right axis malformations (MIM 306955, 208530, 207100)...
  10. Zhu L, Harutyunyan K, Peng J, Wang J, Schwartz R, Belmont J. Identification of a novel role of ZIC3 in regulating cardiac development. Hum Mol Genet. 2007;16:1649-60 pubmed
    Mutations in ZIC3 cause X-linked heterotaxy, a disorder characterized by abnormal lateralization of normally asymmetric thoracic and abdominal organs...
  11. Bedard J, Haaning A, Ware S. Identification of a novel ZIC3 isoform and mutation screening in patients with heterotaxy and congenital heart disease. PLoS ONE. 2011;6:e23755 pubmed publisher
    ..Loss of function of the transcription factor ZIC3 causes X-linked heterotaxy and isolated congenital heart malformations and represents one of the few known ..
  12. Koyabu Y, Nakata K, Mizugishi K, Aruga J, Mikoshiba K. Physical and functional interactions between Zic and Gli proteins. J Biol Chem. 2001;276:6889-92 pubmed
  13. Aruga J, Nagai T, Tokuyama T, Hayashizaki Y, Okazaki Y, Chapman V, et al. The mouse zic gene family. Homologues of the Drosophila pair-rule gene odd-paired. J Biol Chem. 1996;271:1043-7 pubmed
    ..We identified two novel Zic-related genes (Zic2, Zic3) through genomic and cDNA cloning. Both genes are highly similar to Zic(1), especially in their zinc finger motif...
  14. Purandare S, Ware S, Kwan K, Gebbia M, Bassi M, Deng J, et al. A complex syndrome of left-right axis, central nervous system and axial skeleton defects in Zic3 mutant mice. Development. 2002;129:2293-302 pubmed
    ..HTX1 results from mutations in ZIC3, a member of the GLI transcription factor superfamily...
  15. Aruga J, Ogura H, Shutoh F, Ogawa M, Franke B, Nagao S, et al. Locomotor and oculomotor impairment associated with cerebellar dysgenesis in Zic3-deficient (Bent tail) mutant mice. Eur J Neurosci. 2004;20:2159-67 pubmed
    ..The Bent tail mutant mouse was recently shown to lack a submicroscopic part of the X chromosome containing the Zic3 gene, which encodes a zinc-finger protein controlling vertebrate neural development...
  16. Watabe Y, Baba Y, Nakauchi H, Mizota A, Watanabe S. The role of Zic family zinc finger transcription factors in the proliferation and differentiation of retinal progenitor cells. Biochem Biophys Res Commun. 2011;415:42-7 pubmed publisher
    ..b>Zic3 is also expressed in the embryonic retina; its expression level slightly decreases but it is expressed until ..
  17. Krentz A, Murphy M, Zhang T, Sarver A, Jain S, Griswold M, et al. Interaction between DMRT1 function and genetic background modulates signaling and pluripotency to control tumor susceptibility in the fetal germ line. Dev Biol. 2013;377:67-78 pubmed publisher
    ..Given the strong evidence for involvement of DMRT1 in human TGCT, the downstream genes and pathways identified in this study provide potentially useful candidates for roles in the human disease. ..
  18. Assimacopoulos S, Kao T, Issa N, Grove E. Fibroblast growth factor 8 organizes the neocortical area map and regulates sensory map topography. J Neurosci. 2012;32:7191-201 pubmed publisher
    ..Our findings implicate FGF8 as an organizer signal, and its source in the rostromedial telencephalon as an organizer of the neocortical area map. ..
  19. Klootwijk R, Schijvenaars M, Mariman E, Franke B. Further characterization of the genetic defect of the Bent tail mouse, a mouse model for human neural tube defects. Birth Defects Res A Clin Mol Teratol. 2004;70:880-4 pubmed
    ..The mouse mutant is caused by a submicroscopic deletion on Xq that completely encompasses the Zic3 gene...
  20. Gaston Massuet C, Henderson D, Greene N, Copp A. Zic4, a zinc-finger transcription factor, is expressed in the developing mouse nervous system. Dev Dyn. 2005;233:1110-5 pubmed
    ..We conclude that Zic4 has an expression pattern distinct from, but partly overlapping with, other members of the Zic gene family. ..
  21. Miyata T, Nakajima K, Aruga J, Takahashi S, Ikenaka K, Mikoshiba K, et al. Distribution of a reeler gene-related antigen in the developing cerebellum: an immunohistochemical study with an allogeneic antibody CR-50 on normal and reeler mice. J Comp Neurol. 1996;372:215-28 pubmed
    ..The spatiotemporal expressions of the CR-50 antigen in the cerebellum are consistent with the possibility that this antigen is involved in cell-cell interactions related to the histogenetic assembly of Purkinje cells. ..
  22. Lim L, Loh Y, Zhang W, Li Y, Chen X, Wang Y, et al. Zic3 is required for maintenance of pluripotency in embryonic stem cells. Mol Biol Cell. 2007;18:1348-58 pubmed
    ..Here we describe a role for Zic3, a member of the Gli family of zinc finger transcription factors, in the maintenance of pluripotency in ES cells...
  23. Chervenak A, Hakim I, Barald K. Spatiotemporal expression of Zic genes during vertebrate inner ear development. Dev Dyn. 2013;242:897-908 pubmed publisher
    ..Zic expression domains overlap with sites of WNT and SHH signaling during otocyst patterning, suggesting a role for Zic genes in modulating signaling from these pathways. ..
  24. Elliott R, Miller D, Pearsall R, Hohman C, Zhang Y, Poslinski D, et al. Genetic analysis of testis weight and fertility in an interspecies hybrid congenic strain for Chromosome X. Mamm Genome. 2001;12:45-51 pubmed
    ..8 map units for Ihtw1. This region of the genetic map is orthologous to the region on human Chr X containing the gene for the Borjeson-Forssman-Lehman syndrome, an inherited disease in which males show microorchidism. ..
  25. Pearton D, Smith C, Redgate E, van Leeuwen J, Donnison M, Pfeffer P. Elf5 counteracts precocious trophoblast differentiation by maintaining Sox2 and 3 and inhibiting Hand1 expression. Dev Biol. 2014;392:344-57 pubmed publisher
    ..This data thus suggest that Elf5 is a gatekeeper for the TS to differentiated trophoblast transition thereby preventing the precocious differentiation of the undifferentiated extraembryonic ectoderm. ..
  26. Lickert H, Cox B, Wehrle C, Taketo M, Kemler R, Rossant J. Dissecting Wnt/beta-catenin signaling during gastrulation using RNA interference in mouse embryos. Development. 2005;132:2599-609 pubmed
    ..This functional genomic approach allows the rapid identification of functionally important components of embryonic development from large datasets of putative targets. ..
  27. Garber E. "Bent-Tail," A Dominant, Sex-Linked Mutation in the Mouse. Proc Natl Acad Sci U S A. 1952;38:876-9 pubmed
  28. Haaning A, Quinn M, Ware S. Heterotaxy-spectrum heart defects in Zic3 hypomorphic mice. Pediatr Res. 2013;74:494-502 pubmed publisher
    Mutations in Zinc Finger Protein of the Cerebellum 3 (ZIC3) cause X-linked heterotaxy and isolated cardiovascular malformations. Recent data suggest a potential cell-autonomous role for Zic3 in myocardium via regulation of Nppa and Tbx5...
  29. Falconer D. Linkage in the mouse: the sex-linked genes and Rough. Z Indukt Abstamm Vererbungsl. 1954;86:263-8 pubmed
  30. Herrera E, Brown L, Aruga J, Rachel R, Dolen G, Mikoshiba K, et al. Zic2 patterns binocular vision by specifying the uncrossed retinal projection. Cell. 2003;114:545-57 pubmed
    ..These data provide evidence for transcriptional coding of axon pathfinding at the midline. ..
  31. Mizugishi K, Hatayama M, Tohmonda T, Ogawa M, Inoue T, Mikoshiba K, et al. Myogenic repressor I-mfa interferes with the function of Zic family proteins. Biochem Biophys Res Commun. 2004;320:233-40 pubmed
    ..These results suggest that the physical and functional interaction between Zic and I-mfa proteins can play a role in the vertebrate development. ..
  32. Sutherland M, Wang S, Quinn M, Haaning A, Ware S. Zic3 is required in the migrating primitive streak for node morphogenesis and left-right patterning. Hum Mol Genet. 2013;22:1913-23 pubmed publisher
    In humans, loss-of-function mutations in ZIC3 cause isolated cardiovascular malformations and X-linked heterotaxy, a disorder with abnormal left-right asymmetry of organs...
  33. Inoue T, Ogawa M, Mikoshiba K, Aruga J. Zic deficiency in the cortical marginal zone and meninges results in cortical lamination defects resembling those in type II lissencephaly. J Neurosci. 2008;28:4712-25 pubmed publisher
    ..Examination of the expression of Zic genes demonstrated that Zic1, Zic2, and Zic3 were expressed by the progenitor cells in the septum and cortical hem, the sites of generation of the Cajal-Retzius ..
  34. Lyon M. Order of loci on the X-chromosome of the mouse. Genet Res. 1966;7:130-3 pubmed
  35. Ahmed J, Ali R, Warr N, Wilson H, Bellchambers H, Barratt K, et al. A murine Zic3 transcript with a premature termination codon evades nonsense-mediated decay during axis formation. Dis Model Mech. 2013;6:755-67 pubmed publisher
    The ZIC transcription factors are key mediators of embryonic development and ZIC3 is the gene most commonly associated with situs defects (heterotaxy) in humans. Half of patient ZIC3 mutations introduce a premature termination codon (PTC)...
  36. Johnson D. The interfrontal bone and mutant genes in the mouse. J Anat. 1976;121:507-13 pubmed
    ..All genes reviewed which increase the incidence of the interfrontal bone and affect the neural tube also change the proportions of the adult skull. ..
  37. Feng W, Leach S, Tipney H, Phang T, Geraci M, Spritz R, et al. Spatial and temporal analysis of gene expression during growth and fusion of the mouse facial prominences. PLoS ONE. 2009;4:e8066 pubmed publisher
    ..Overall, our studies provide a valuable resource for probing orofacial development and a robust dataset for bioinformatic analysis of spatial and temporal gene expression changes during embryogenesis. ..
  38. Sone M, Morone N, Nakamura T, Tanaka A, Okita K, Woltjen K, et al. Hybrid Cellular Metabolism Coordinated by Zic3 and Esrrb Synergistically Enhances Induction of Naive Pluripotency. Cell Metab. 2017;25:1103-1117.e6 pubmed publisher
    ..Here, we show that when transduced with Oct4, Sox2, and Klf4 (OSK) into murine fibroblasts, Zic3 and Esrrb synergistically enhance the reprogramming efficiency by regulating cellular metabolic pathways...
  39. Lusis A, West J. X-linked and autosomal genes controlling mouse alpha-galactosidase expression. Genetics. 1978;88:327-42 pubmed
    ..Among certain recombinant inbred lines, the variation appears to segregate as a single major locus. ..
  40. Inoue T, Hatayama M, Tohmonda T, Itohara S, Aruga J, Mikoshiba K. Mouse Zic5 deficiency results in neural tube defects and hypoplasia of cephalic neural crest derivatives. Dev Biol. 2004;270:146-62 pubmed
    ..Based on both their similar expression pattern in mouse embryos and the malformations observed in Zic5-deficient mutant mice, human ZIC5 might be involved in the deletion syndrome. ..
  41. Lyon M, Searle A, Ford C, Ohno S. A MOUSE TRANSLOCATION SUPPRESSING SEX-LINKED VARIEGATION. Cytogenetics. 1964;3:306-23 pubmed
  42. Huijing F, Eicher E, Coleman D. Location of phosphorylase kinase (Phk) in the mouse X chromosome. Biochem Genet. 1973;9:193-6 pubmed
  43. Iwafuchi Doi M, Matsuda K, Murakami K, Niwa H, Tesar P, Aruga J, et al. Transcriptional regulatory networks in epiblast cells and during anterior neural plate development as modeled in epiblast stem cells. Development. 2012;139:3926-37 pubmed publisher
    ..The direct interaction of these factors with enhancers of Otx2, Hesx1 and Sox2 genes was demonstrated. Thus, a combination of regulatory processes that suppresses non-ANP lineages and promotes neural plate development determines the ANP...
  44. Pan H, Gustafsson M, Aruga J, Tiedken J, Chen J, Emerson C. A role for Zic1 and Zic2 in Myf5 regulation and somite myogenesis. Dev Biol. 2011;351:120-7 pubmed publisher
    ..In functional reporter assays, Zic1 and Zic2, but not Zic3, potentiate the transactivation of Gli-dependent Myf5 epaxial somite-specific (ES) enhancer activity in 3T3 cells, ..
  45. Franke B, Klootwijk R, Lemmers B, de Kovel C, Steegers Theunissen R, Mariman E. Phenotype of the neural tube defect mouse model bent tail is not sensitive to maternal folinic acid, myo-inositol, or zinc supplementation. Birth Defects Res A Clin Mol Teratol. 2003;67:979-84 pubmed
    ..by a submicroscopic deletion that completely encompasses the gene coding for the zinc finger transcription factor Zic3. In this study we investigated the sensitivity of the phenotype of Bent tail to the nutrients folinic acid, myo-..
  46. Hilger A, Halbritter J, Pennimpede T, van der Ven A, Sarma G, Braun D, et al. Targeted Resequencing of 29 Candidate Genes and Mouse Expression Studies Implicate ZIC3 and FOXF1 in Human VATER/VACTERL Association. Hum Mutat. 2015;36:1150-4 pubmed publisher
    ..targeted resequencing of 25 ciliary candidate genes as well as disease-associated genes (FOXF1, HOXD13, PTEN, ZIC3) in 123 patients with VATER/VACTERL or VATER/VACTERL-like phenotype...
  47. Eicher E, Southard J, Scriver C, Glorieux F. Hypophosphatemia: mouse model for human familial hypophosphatemic (vitamin D-resistant) rickets. Proc Natl Acad Sci U S A. 1976;73:4667-71 pubmed
    ..The mouse model should facilitate study of the defect in transport of plasma inorganic phosphate anion. ..
  48. Maier J, Harfe B. Nuclei pulposi formation from the embryonic notochord occurs normally in GDF-5-deficient mice. Spine (Phila Pa 1976). 2011;36:E1555-61 pubmed publisher
    ..The use of mouse alleles to mark cells that produce all cell types that reside in the adult nucleus pulposus will allow for a detailed examination of disc formation in other mouse mutants that have been reported to contain disc defects. ..
  49. Zhao W, Jiang B, Hu H, Zhang S, Lv S, Yuan J, et al. Lack of CUL4B leads to increased abundance of GFAP-positive cells that is mediated by PTGDS in mouse brain. Hum Mol Genet. 2015;24:4686-97 pubmed publisher
    ..We further observed that Ptgds is targeted and repressed by the CUL4B/PRC2 complex. Together, our results demonstrate CUL4B as a negative regulator of GFAP expression during neural development. ..
  50. Qin S, Ware S, Waclaw R, Campbell K. Septal contributions to olfactory bulb interneuron diversity in the embryonic mouse telencephalon: role of the homeobox gene Gsx2. Neural Dev. 2017;12:13 pubmed publisher
    ..In this study, we utilized Zic3-lacZ and Gsx2e-CIE transgenic mice as genetic fate-mapping tools to study OB interneuron contributions derived from ..