Disease relevance of Zic1

• However, in open brain, a mutant with severe neural tube defects, and in the Wnt-3a mutant mice, the expression of Zic genes was changed [1].
• Furthermore, Zic protein was detected in medulloblastoma (26/29 cases), whereas no other tumors examined (over 70 cases including primitive neuroectodermal tumors) expressed this protein [2].
• Development of holoprosencephaly, forebrain anomalies, and cerebellar dysgenesis indicate that region-specific morphogenesis of the CNS is also controlled by Zic genes [3].

High impact information on Zic1

• Although the Bent tail phenotype probably is the result of the deletion 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 [4].
• Multiple functions of a Zic-like gene in the differentiation of notochord, central nervous system and muscle in Ciona savignyi embryos [5].
• These findings suggest that Zic1 may determine the cerebellar folial pattern principally via regulation of cell proliferation in the EGL [6].
• Zic genes encode zinc finger proteins, the expression of which is highly restricted to cerebellar granule cells and their precursors [6].
• The nucleotide sequence of human Zic cDNA is 85% homologous to that of mouse Zic cDNA [2].

Biological context of Zic1

• The chromosomal location of Zic4 was determined to be mouse chromosome 9 in the vicinity of Zic1, using an interspecific backcross panel [7].
• The mouse Zic genes encode zinc-finger (Zf) proteins expressed only in the cerebellum of the adult brain [7].
• They are very similar to mouse Zic1 and Zic2 in the protein coding region including the zinc finger domain [8].
• Conversely, we observed a significant cell number reduction without loss of dorsal properties in the dorsal spinal cords of Zic1-deficient mice [9].
• PAX3 encodes a transcription factor, which with Zic1 is necessary for induction of the neural crest during early embryonic development [10].

Anatomical context of Zic1

• 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 [11].
• Both Zic1 and Zic2 are expressed in the precursor cells of the granule neuron and the neurons in cerebellar nuclei [11].
• Our findings suggest that Zic1 and Zic2 have essentially the same properties as Zic3 and that the Xenopus Zic family may act cooperatively in the initial phase of neural and neural crest development [8].
• In early gastrula, Zic1 expression was restricted to the prospective neural plate region whereas Zic2 was expressed widely in the ectoderm [8].
• Zic1 promotes the expansion of dorsal neural progenitors in spinal cord by inhibiting neuronal differentiation [9].

Regulatory relationships of Zic1

• Zic2 controls cerebellar development in cooperation with Zic1 [11].
• Zic1 regulates the patterning of vertebral arches in cooperation with Gli3 [12].
• Consequently, I-mfa inhibited transcriptional activation by the Zic proteins in cultured cells [13].

Other interactions of Zic1

• We examined the expression of Zic1, Zic2, and Zic3 genes in the mouse embryo by means of in situ hybridization [1].
• Whereas the embryonic expression patterns of Zic1, 2, 3, and 5 have been described in detail, Zic4 has not yet received close attention [14].
• The Zic1/Gli3 double mutants showed severe abnormalities of vertebral arches not found in single mutants [12].
• In the present study, we characterized the fifth member of the mouse Zic family gene, mouse Zic5 [15].
• The changed expression pattern in Wnt-3a mutant mice suggests that Zic genes in the neural tube are regulated by the factors from notochord [1].

Analytical, diagnostic and therapeutic context of Zic1

• A novel gene, Dorz1, was identified and characterized as one of the most significantly down-regulated genes in Zic1-deficient cerebellum by the DNA microarray analysis [16].

References