The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

Zic2  -  zinc finger protein of the cerebellum 2

Mus musculus

Synonyms: GENA 29, HPE5, Ku, Zinc finger protein ZIC 2, Zinc finger protein of the cerebellum 2, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Zic2

  • Mutation of human and mouse Zic2 is associated 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 [1].
  • Here we show that reduced expression (knockdown) of mouse Zic2 causes neurulation delay, resulting in HPE and spina bifida [2].
  • The biochemical properties of this negative-acting factor closely resemble those of the Ku antigen, a human nuclear DNA-binding heterodimer which is the target of autoantibodies in several autoimmune diseases [3].
  • Heat shock selectively inhibits ribosomal RNA gene transcription and down-regulates E1BF/Ku in mouse lymphosarcoma cells [4].
  • To investigate the involvement of these proteins in DNA fragmentation after ischemia/reperfusion, Ku protein expression was examined before and after transient focal cerebral ischemia (FCI) in mice [5].

High impact information on Zic2

  • We conclude that Isl2 specifies RGC laterality by repressing an ipsilateral pathfinding program unique to VTC RGCs and involving Zic2 and EphB1 [6].
  • Loss- and gain-of-function analyses indicate that Zic2 is necessary and sufficient to regulate RGC axon repulsion by cues at the optic chiasm midline [7].
  • Zic2 patterns binocular vision by specifying the uncrossed retinal projection [7].
  • Zic2 regulates the kinetics of neurulation [2].
  • DNA-dependent protein kinase (DNA-PK) consists of a heterodimeric protein (Ku) and a large catalytic subunit (DNA-PKcs) [8].

Biological context of Zic2

  • Here, we show that the zinc finger transcription factor Zic2, a vertebrate homolog of the Drosophila gene odd-paired, is expressed in RGCs with an uncrossed trajectory during the period when this subpopulation grows from the ventrotemporal retina toward the optic chiasm [7].
  • They are very similar to mouse Zic1 and Zic2 in the protein coding region including the zinc finger domain [9].
  • Published information indicates that Zic2 expression is most prominent in the dorsal neural tube/spinal cord and in the hindbrain; however, there is no published description of the pattern of expression of Zic2 in the developing forebrain where the main Zic2 associated phenotype occurs [10].
  • Interestingly, besides their role in DSB repair, Ku proteins bind to chromosome ends, or telomeres, protecting them from end-to-end fusions [11].
  • scid cells are deficient in Ku and replication protein A phosphorylation by the DNA-dependent protein kinase [12].

Anatomical context of Zic2

  • However, the disruption of Zic1, a strong homolog of Zic2 that has an overlapping expression pattern, results in cerebellar malformation with no apparent abnormalities in the forebrain or in posterior neuropore closure [13].
  • During primitive streak stages Zic2 is expressed transiently and uniquely in the node and the head process mesendoderm [1].
  • Both Zic1 and Zic2 are expressed in the precursor cells of the granule neuron and the neurons in cerebellar nuclei [13].
  • Additionally Zic2 is required during hindbrain patterning for the normal development of rhombomeres 3 and 5 [14].
  • Zic2 is required for neural crest formation and hindbrain patterning during mouse development [14].

Associations of Zic2 with chemical compounds


Regulatory relationships of Zic2

  • Zic2 controls cerebellar development in cooperation with Zic1 [13].

Other interactions of Zic2

  • For all stages, significant differences in the spatial expression of Zic1, Zic2, and Zic3 were observed [17].
  • Reduced expression of Zic2 in mice results in spina bifida and holoprosencephaly [13].
  • The transcription factor Zic2 and guidance receptor EphB1, required by RGCs to project ipsilaterally, colocalize in RGCs distinct from Isl2 RGCs in the ventral-temporal crescent (VTC), the source of ipsilateral projections [6].
  • A search for proteins binding to the amino terminal domain of Zic2 revealed that inhibitor of MyoD family (I-mfa) protein, which has been identified as a repressor of myogenic helix-loop-helix class transcription factors, can physically interact with the amino terminal domain [18].

Analytical, diagnostic and therapeutic context of Zic2

  • Northern blotting and ribonuclease protection showed that Zic2 and Zic3 are expressed in a restricted manner in the cerebellum at the adult stage [19].
  • We examined the expression of Zic1, Zic2, and Zic3 genes in the mouse embryo by means of in situ hybridization [17].
  • In resistant cells, electrophoretic mobility shift assays revealed an increased DNA-end binding activity that could be ascribed, by supershifting the retardation complexes with antibodies, to the autoantigen Ku [15].
  • Western-blot analysis with antibodies specific for the two subunits of Ku protein showed the absence of p72 subunit after 3 h of heat shock [4].
  • Ku itself is probably involved in stabilizing broken DNA ends, bringing them together and preparing them for ligation [16].


  1. Overlapping and distinct expression domains of Zic2 and Zic3 during mouse gastrulation. Elms, P., Scurry, A., Davies, J., Willoughby, C., Hacker, T., Bogani, D., Arkell, R. Gene Expr. Patterns (2004) [Pubmed]
  2. Zic2 regulates the kinetics of neurulation. Nagai, T., Aruga, J., Minowa, O., Sugimoto, T., Ohno, Y., Noda, T., Mikoshiba, K. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  3. The nucleolar transcription activator UBF relieves Ku antigen-mediated repression of mouse ribosomal gene transcription. Kuhn, A., Stefanovsky, V., Grummt, I. Nucleic Acids Res. (1993) [Pubmed]
  4. Heat shock selectively inhibits ribosomal RNA gene transcription and down-regulates E1BF/Ku in mouse lymphosarcoma cells. Ghoshal, K., Jacob, S.T. Biochem. J. (1996) [Pubmed]
  5. Early decrease in dna repair proteins, Ku70 and Ku86, and subsequent DNA fragmentation after transient focal cerebral ischemia in mice. Kim, G.W., Noshita, N., Sugawara, T., Chan, P.H. Stroke (2001) [Pubmed]
  6. Magnitude of binocular vision controlled by islet-2 repression of a genetic program that specifies laterality of retinal axon pathfinding. Pak, W., Hindges, R., Lim, Y.S., Pfaff, S.L., O'Leary, D.D. Cell (2004) [Pubmed]
  7. Zic2 patterns binocular vision by specifying the uncrossed retinal projection. Herrera, E., Brown, L., Aruga, J., Rachel, R.A., Dolen, G., Mikoshiba, K., Brown, S., Mason, C.A. Cell (2003) [Pubmed]
  8. Identification of a nonsense mutation in the carboxyl-terminal region of DNA-dependent protein kinase catalytic subunit in the scid mouse. Blunt, T., Gell, D., Fox, M., Taccioli, G.E., Lehmann, A.R., Jackson, S.P., Jeggo, P.A. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  9. Xenopus Zic family and its role in neural and neural crest development. Nakata, K., Nagai, T., Aruga, J., Mikoshiba, K. Mech. Dev. (1998) [Pubmed]
  10. Immunolocalization of Zic2 expression in the developing mouse forebrain. Brown, L.Y., Kottmann, A.H., Brown, S. Gene Expr. Patterns (2003) [Pubmed]
  11. The absence of the dna-dependent protein kinase catalytic subunit in mice results in anaphase bridges and in increased telomeric fusions with normal telomere length and G-strand overhang. Goytisolo, F.A., Samper, E., Edmonson, S., Taccioli, G.E., Blasco, M.A. Mol. Cell. Biol. (2001) [Pubmed]
  12. scid cells are deficient in Ku and replication protein A phosphorylation by the DNA-dependent protein kinase. Boubnov, N.V., Weaver, D.T. Mol. Cell. Biol. (1995) [Pubmed]
  13. Zic2 controls cerebellar development in cooperation with Zic1. Aruga, J., Inoue, T., Hoshino, J., Mikoshiba, K. J. Neurosci. (2002) [Pubmed]
  14. Zic2 is required for neural crest formation and hindbrain patterning during mouse development. Elms, P., Siggers, P., Napper, D., Greenfield, A., Arkell, R. Dev. Biol. (2003) [Pubmed]
  15. Cross-resistance to ionizing radiation in a murine leukemic cell line resistant to cis-dichlorodiammineplatinum(II): role of Ku autoantigen. Frit, P., Canitrot, Y., Muller, C., Foray, N., Calsou, P., Marangoni, E., Bourhis, J., Salles, B. Mol. Pharmacol. (1999) [Pubmed]
  16. Ku, a DNA repair protein with multiple cellular functions? Featherstone, C., Jackson, S.P. Mutat. Res. (1999) [Pubmed]
  17. The expression of the mouse Zic1, Zic2, and Zic3 gene suggests an essential role for Zic genes in body pattern formation. Nagai, T., Aruga, J., Takada, S., Günther, T., Spörle, R., Schughart, K., Mikoshiba, K. Dev. Biol. (1997) [Pubmed]
  18. Myogenic repressor I-mfa interferes with the function of Zic family proteins. Mizugishi, K., Hatayama, M., Tohmonda, T., Ogawa, M., Inoue, T., Mikoshiba, K., Aruga, J. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  19. The mouse zic gene family. Homologues of the Drosophila pair-rule gene odd-paired. Aruga, J., Nagai, T., Tokuyama, T., Hayashizaki, Y., Okazaki, Y., Chapman, V.M., Mikoshiba, K. J. Biol. Chem. (1996) [Pubmed]
WikiGenes - Universities