Gene Symbol: Zic1
Description: zinc finger protein of the cerebellum 1
Alias: ZIC, ZNF201, zinc finger protein ZIC 1, Zic family member 1 (odd-paired homolog, Drosophila), odd-paired homolog
Species: mouse
Products:     Zic1

Top Publications

  1. Aldinger K, Lehmann O, Hudgins L, Chizhikov V, Bassuk A, Ades L, et al. FOXC1 is required for normal cerebellar development and is a major contributor to chromosome 6p25.3 Dandy-Walker malformation. Nat Genet. 2009;41:1037-42 pubmed publisher
    ..Our results highlight a previously unrecognized role for mesenchyme-neuroepithelium interactions in the mid-hindbrain during early embryogenesis...
  2. Schüller U, Heine V, Mao J, Kho A, Dillon A, Han Y, et al. Acquisition of granule neuron precursor identity is a critical determinant of progenitor cell competence to form Shh-induced medulloblastoma. Cancer Cell. 2008;14:123-34 pubmed publisher
    ..Thus, oncogenic Hh signaling promotes medulloblastoma from lineage-restricted granule cell progenitors. ..
  3. 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 ..
  4. Daneman R, Zhou L, Kebede A, Barres B. Pericytes are required for blood-brain barrier integrity during embryogenesis. Nature. 2010;468:562-6 pubmed publisher
    ..These data indicate that pericyte-endothelial cell interactions are critical to regulate the BBB during development, and disruption of these interactions may lead to BBB dysfunction and neuroinflammation during CNS injury and disease...
  5. 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...
  6. Matsushima D, Heavner W, Pevny L. Combinatorial regulation of optic cup progenitor cell fate by SOX2 and PAX6. Development. 2011;138:443-54 pubmed publisher
    ..Collectively, these results demonstrate that precise regulation of the ratio of SOX2 to PAX6 is necessary to ensure accurate progenitor cell specification, and place SOX2 as a decisive factor of neural competence in the retina. ..
  7. 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. ..
  8. Roux M, Laforest B, Eudes N, Bertrand N, Stefanovic S, Zaffran S. Hoxa1 and Hoxb1 are required for pharyngeal arch artery development. Mech Dev. 2017;143:1-8 pubmed publisher
    ..Together, our data reveal a critical role for anterior Hox genes during PAA development, providing new mechanistic insights into the etiology of congenital heart defects. ..
  9. Ogura H, Aruga J, Mikoshiba K. Behavioral abnormalities of Zic1 and Zic2 mutant mice: implications as models for human neurological disorders. Behav Genet. 2001;31:317-24 pubmed
    b>Zic1 and Zic2 encode closely related zinc finger proteins expressed in dorsal neural tube and its derivatives...

More Information


  1. Kim E, Wang Y, Kim S, Bornhorst M, Jecrois E, Anthony T, et al. Transient inhibition of the ERK pathway prevents cerebellar developmental defects and improves long-term motor functions in murine models of neurofibromatosis type 1. elife. 2014;3: pubmed publisher
  2. Aruga J, Inoue T, Hoshino J, Mikoshiba K. Zic2 controls cerebellar development in cooperation with Zic1. J Neurosci. 2002;22:218-25 pubmed
    ..Reduced expression of Zic2 in mice results in spina bifida and holoprosencephaly. However, the disruption of Zic1, a strong homolog of Zic2 that has an overlapping expression pattern, results in cerebellar malformation with no ..
  3. Hoffmann A, Yang X, Burnicka Turek O, Bosman J, Ren X, Steimle J, et al. Foxf genes integrate tbx5 and hedgehog pathways in the second heart field for cardiac septation. PLoS Genet. 2014;10:e1004604 pubmed publisher
  4. Jochheim Richter A, Rüdrich U, Koczan D, Hillemann T, Tewes S, Petry M, et al. Gene expression analysis identifies novel genes participating in early murine liver development and adult liver regeneration. Differentiation. 2006;74:167-73 pubmed
    ..were exclusively detected at 24 hr, whereas the genes Twist1, Midkine, and zinc finger protein of cerebellum 1 (Zic1) each showed a specific expression profile in the regenerating liver with peak expressions at 4, 24, and 6 hr, ..
  5. 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
    ..b>Zic1, Zic2, and Zic3 were determined to mouse chromosome 9, 14, and X using an interspecific backcross panel...
  6. Di Giovannantonio L, Di Salvio M, Omodei D, Prakash N, Wurst W, Pierani A, et al. Otx2 cell-autonomously determines dorsal mesencephalon versus cerebellum fate independently of isthmic organizing activity. Development. 2014;141:377-88 pubmed publisher
    ..We found that the Pax7(+) m1 domain can be further subdivided into a dorsal Zic1(+) m1a and a ventral Zic1(-) m1b sub-domain...
  7. Aruga J, Minowa O, Yaginuma H, Kuno J, Nagai T, Noda T, et al. Mouse Zic1 is involved in cerebellar development. J Neurosci. 1998;18:284-93 pubmed
    ..These genes are homologs of the Drosophila pair-rule gene odd-paired. To clarify the role of the Zic1 gene, we have generated mice deficient in Zic1...
  8. Siegenthaler J, Choe Y, Patterson K, Hsieh I, Li D, Jaminet S, et al. Foxc1 is required by pericytes during fetal brain angiogenesis. Biol Open. 2013;2:647-59 pubmed publisher
    ..Collectively these data point towards an important role for Foxc1 in certain brain pericyte functions (e.g. vessel morphogenesis) but not others (e.g. barriergenesis). ..
  9. Chervenak A, Bank L, Thomsen N, Glanville Jones H, Jonathan S, Millen K, et al. The role of Zic genes in inner ear development in the mouse: Exploring mutant mouse phenotypes. Dev Dyn. 2014;243:1487-98 pubmed publisher
    Murine Zic genes (Zic1-5) are expressed in the dorsal hindbrain and in periotic mesenchyme (POM) adjacent to the developing inner ear...
  10. Wang B, Harrison W, Overbeek P, Zheng H. Transposon mutagenesis with coat color genotyping identifies an essential role for Skor2 in sonic hedgehog signaling and cerebellum development. Development. 2011;138:4487-97 pubmed publisher
    ..Our study identifies an essential function for Skor2 as a novel transcriptional regulator in Purkinje cells that acts upstream of Shh during cerebellum development. ..
  11. Urban S, Kobi D, Ennen M, Langer D, Le Gras S, Ye T, et al. A Brn2-Zic1 axis specifies the neuronal fate of retinoic-acid-treated embryonic stem cells. J Cell Sci. 2015;128:2303-18 pubmed publisher
    ..defined the core of the Brn2-regulated neuronal programme, among which was that encoding the transcription factor Zic1. Small hairpin RNA (shRNA)-mediated silencing of Zic1 prevented ESCs from differentiating into neuronal precursors, ..
  12. Chizhikov V, Davenport J, Zhang Q, Shih E, Cabello O, Fuchs J, et al. Cilia proteins control cerebellar morphogenesis by promoting expansion of the granule progenitor pool. J Neurosci. 2007;27:9780-9 pubmed
  13. Dahmane N, Ruiz i Altaba A. Sonic hedgehog regulates the growth and patterning of the cerebellum. Development. 1999;126:3089-100 pubmed
    ..In addition, they provide a cellular context for medulloblastomas, childhood cancers of the cerebellum. ..
  14. García Moreno F, Pedraza M, Di Giovannantonio L, Di Salvio M, López Mascaraque L, Simeone A, et al. A neuronal migratory pathway crossing from diencephalon to telencephalon populates amygdala nuclei. Nat Neurosci. 2010;13:680-9 pubmed publisher
    ..The diencephalic transcription factor OTP was necessary for this migratory behavior. ..
  15. 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
    b>Zic family genes encode zinc finger proteins, which are homologues of the Drosophila pair-rule gene odd-paired. In the present study, we characterized the fifth member of the mouse Zic family gene, mouse Zic5...
  16. Grinberg I, Northrup H, Ardinger H, Prasad C, Dobyns W, Millen K. Heterozygous deletion of the linked genes ZIC1 and ZIC4 is involved in Dandy-Walker malformation. Nat Genet. 2004;36:1053-5 pubmed
    ..defined the first critical region associated with DWM, encompassing two adjacent Zinc finger in cerebellum genes, ZIC1 and ZIC4...
  17. Chervenak A, Hakim I, Barald K. Spatiotemporal expression of Zic genes during vertebrate inner ear development. Dev Dyn. 2013;242:897-908 pubmed publisher
    ..These signals include SHH, FGFs, BMPs, and WNTs from the hindbrain and SHH from the notochord. Zic genes, which are expressed in the dorsal neural tube and act during neural development, have been implicated as ..
  18. Müller Smith K, Williamson T, Schwartz M, Vaccarino F. Impaired motor coordination and disrupted cerebellar architecture in Fgfr1 and Fgfr2 double knockout mice. Brain Res. 2012;1460:12-24 pubmed publisher
    ..The disrupted cerebellar size and laminar architecture resulting from loss of FGFR signaling impair motor learning and coordination in FGFR DKO mice. ..
  19. He L, Yu K, Lu F, Wang J, Wu L, Zhao C, et al. Transcriptional Regulator ZEB2 Is Essential for Bergmann Glia Development. J Neurosci. 2018;38:1575-1587 pubmed publisher
    ..This finding demonstrates a previously unrecognized critical role for ZEB2 in Bergmann glia specification, and points to an important contribution of ZEB2 dysfunction to cerebellar motor disorders in Mowat-Wilson syndrome. ..
  20. 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
    ..Both types of CR-50-labeled cells were positive for a DNA-binding protein, zic. By treating living cerebellar slices with CR-50, the extracellular antigen was localized as a puncutate staining ..
  21. 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
    Zic family zinc-finger proteins play various roles in animal development. In mice, five Zic genes (Zic1-5) have been reported...
  22. 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. ..
  23. 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
    ..polymerase chain reaction using mRNA from the retina at various developmental stages showed that Zic1 and Zic2 are expressed in the embryonic retina and then gradually disappear during retinal development...
  24. 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
    ..Whereas the embryonic expression patterns of Zic1, 2, 3, and 5 have been described in detail, Zic4 has not yet received close attention...
  25. 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...
  26. Zhang P, Ha T, Larouche M, Swanson D, Goldowitz D. Kruppel-Like Factor 4 Regulates Granule Cell Pax6 Expression and Cell Proliferation in Early Cerebellar Development. PLoS ONE. 2015;10:e0134390 pubmed publisher
    ..This paper is the first to describe a role for Klf4 in the cerebellum and provides insight into this gene's function in neuronal development. ..
  27. Engelkamp D, Rashbass P, Seawright A, van Heyningen V. Role of Pax6 in development of the cerebellar system. Development. 1999;126:3585-96 pubmed
    ..Our results suggest that Pax6 plays a strong role during hindbrain migration processes and at least part of its activity is mediated through regulation of the netrin receptor Unc5h3. ..
  28. Friedel R, Kerjan G, Rayburn H, Schüller U, Sotelo C, Tessier Lavigne M, et al. Plexin-B2 controls the development of cerebellar granule cells. J Neurosci. 2007;27:3921-32 pubmed
    ..Many differentiated granule cells migrate inside the cerebellum and keep proliferating. These results reveal that Plexin-B2 controls the balance between proliferation and differentiation in granule cells. ..
  29. Tong K, Kwan K. Common partner Smad-independent canonical bone morphogenetic protein signaling in the specification process of the anterior rhombic lip during cerebellum development. Mol Cell Biol. 2013;33:1925-37 pubmed publisher
    ..Our results demonstrate functional redundancy for Smad1 and Smad5 but functional discrepancy between Smad1/5 and Smad4 during cerebellum development. ..
  30. 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
    ..When Zic1-3 and I-mfa proteins were co-expressed in cultured cells, nuclear import of the Zic proteins was inhibited...
  31. Lewis P, Gritli Linde A, Smeyne R, Kottmann A, McMahon A. Sonic hedgehog signaling is required for expansion of granule neuron precursors and patterning of the mouse cerebellum. Dev Biol. 2004;270:393-410 pubmed
    ..Together, these findings provide additional evidence for Shh's key regulatory role in controlling growth of the cerebellar primordium. ..
  32. Aruga J, Tohmonda T, Homma S, Mikoshiba K. Zic1 promotes the expansion of dorsal neural progenitors in spinal cord by inhibiting neuronal differentiation. Dev Biol. 2002;244:329-41 pubmed
    The role of Zic1 was investigated by altering its expression status in developing spinal cords. Zic genes encode zinc finger proteins homologous to Drosophila Odd-paired...
  33. Hägglund A, Jones I, Carlsson L. A novel mouse model of anterior segment dysgenesis (ASD): conditional deletion of Tsc1 disrupts ciliary body and iris development. Dis Model Mech. 2017;10:245-257 pubmed publisher
  34. Arnold T, Niaudet C, Pang M, Siegenthaler J, Gaengel K, Jung B, et al. Excessive vascular sprouting underlies cerebral hemorrhage in mice lacking αVβ8-TGFβ signaling in the brain. Development. 2014;141:4489-99 pubmed publisher
    ..Our data therefore suggest that abnormal vascular sprouting and patterning, not BBB dysfunction, underlie developmental cerebral hemorrhage. ..
  35. Cabrera R, Finnell R, Zhu H, Shaw G, Wlodarczyk B. Transcriptional analyses of two mouse models of spina bifida. Birth Defects Res A Clin Mol Teratol. 2012;94:782-9 pubmed publisher
    ..two genes that showed decreased expression in both mutants were v-ski sarcoma viral oncogene homolog (Ski), and Zic1, a transcription factor member of the zinc finger family...
  36. Walcher T, Xie Q, Sun J, Irmler M, Beckers J, Oztürk T, et al. Functional dissection of the paired domain of Pax6 reveals molecular mechanisms of coordinating neurogenesis and proliferation. Development. 2013;140:1123-36 pubmed publisher
    ..Thus, Pax6 achieves its key roles in the developing forebrain by utilizing particular subdomains to coordinate patterning, neurogenesis and proliferation simultaneously. ..
  37. Hoshino J, Aruga J, Ishiguro A, Mikoshiba K. Dorz1, a novel gene expressed in differentiating cerebellar granule neurons, is down-regulated in Zic1-deficient mouse. Brain Res Mol Brain Res. 2003;120:57-64 pubmed
    The Zic1 gene encodes a zinc finger protein that controls vertebrate neural development...
  38. Heavner W, Andoniadou C, Pevny L. Establishment of the neurogenic boundary of the mouse retina requires cooperation of SOX2 and WNT signaling. Neural Dev. 2014;9:27 pubmed publisher
  39. Wong R, Wlodarczyk B, Min K, Scott M, Kartiko S, Yu W, et al. Mouse Fkbp8 activity is required to inhibit cell death and establish dorso-ventral patterning in the posterior neural tube. Hum Mol Genet. 2008;17:587-601 pubmed
    ..The mutant Fkbp8 allele is a new experimental model which will be useful in dissecting the pathogenesis of spinal NTDs, and enhance our understanding of the etiology of human NTDs...
  40. He X, Zhang L, Chen Y, Remke M, Shih D, Lu F, et al. The G protein α subunit Gαs is a tumor suppressor in Sonic hedgehog-driven medulloblastoma. Nat Med. 2014;20:1035-42 pubmed publisher
  41. Otero J, Kalaszczynska I, Michowski W, Wong M, Gygli P, Gokozan H, et al. Cerebellar cortical lamination and foliation require cyclin A2. Dev Biol. 2014;385:328-39 pubmed publisher
    ..Although cyclin E1 has been reported to compensate for cyclin A2 function in fibroblasts and is upregulated in cyclin A2 null cerebella, cyclin E1 expression was unable to compensate for loss-of cyclin A2 function. ..
  42. Himeda C, Barro M, Emerson C. Pax3 synergizes with Gli2 and Zic1 in transactivating the Myf5 epaxial somite enhancer. Dev Biol. 2013;383:7-14 pubmed publisher
    ..We show that Pax3 synergizes with both Gli2 and Zic1 in transactivating the Myf5 epaxial somite (ES) enhancer in concert with the Myf5 promoter...
  43. Rhinn M, Schuhbaur B, Niederreither K, Dolle P. Involvement of retinol dehydrogenase 10 in embryonic patterning and rescue of its loss of function by maternal retinaldehyde treatment. Proc Natl Acad Sci U S A. 2011;108:16687-92 pubmed publisher
    ..These results underscore the importance of maternal retinoids in preventing congenital birth defects, and lead to a revised model of the importance of RDH10 and RALDHs in controlling embryonic RA distribution...
  44. Cho K, Lee J, Kim K, Lee E, Suh J, Lee H, et al. Fine mapping of the circling (cir) gene on the distal portion of mouse chromosome 9. Comp Med. 2003;53:642-8 pubmed
    ..Therefore, the circling mouse is a potential animal model for DFNB6 deafness in humans. ..
  45. 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. ..
  46. Liu G, Terzian T, Xiong S, Van Pelt C, Audiffred A, Box N, et al. The p53-Mdm2 network in progenitor cell expansion during mouse postnatal development. J Pathol. 2007;213:360-8 pubmed
  47. Koirala S, Jin Z, Piao X, Corfas G. GPR56-regulated granule cell adhesion is essential for rostral cerebellar development. J Neurosci. 2009;29:7439-49 pubmed publisher
    ..These studies establish a novel role for GPR56 in the adhesion of developing neurons to basal lamina molecules and suggest that this adhesion is critical for maintenance of the pia and proper cerebellar morphogenesis. ..
  48. Higginbotham H, Guo J, Yokota Y, Umberger N, Su C, Li J, et al. Arl13b-regulated cilia activities are essential for polarized radial glial scaffold formation. Nat Neurosci. 2013;16:1000-7 pubmed publisher
  49. Nieman B, Blank M, Roman B, Henkelman R, Millen K. If the skull fits: magnetic resonance imaging and microcomputed tomography for combined analysis of brain and skull phenotypes in the mouse. Physiol Genomics. 2012;44:992-1002 pubmed publisher
  50. 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
    b>Zic and Gli family proteins are transcription factors that share similar zinc finger domains. Recent studies indicate that Zic and Gli collaborate in neural and skeletal development...
  51. Garcia Frigola C, Herrera E. Zic2 regulates the expression of Sert to modulate eye-specific refinement at the visual targets. EMBO J. 2010;29:3170-83 pubmed publisher
    ..These results link, at the molecular level, early events in neural differentiation with late activity-dependent processes and propose a mechanism for the establishment of eye-specific domains at the visual targets. ..
  52. 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 situ hybridization studies show that Zic1, 2, and 3 transcripts are expressed in Myf5-expressing epaxial myogenic progenitors in the dorsal medial ..
  53. Cheng L, Zhang J, Reed R. The transcription factor Zfp423/OAZ is required for cerebellar development and CNS midline patterning. Dev Biol. 2007;307:43-52 pubmed
    ..Moreover, there are malformations in midline structures including the septum, thalamus and hypothalamus, suggesting a pivotal role of OAZ in CNS midline patterning. ..