Molecular basis of Zic-mediated developmental control

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Zic genes are known for causal genes of holoprosencephaly, Dandy-Walker malformation, and heterotasxy.. In this study, following points of the Zic gene family have been dealt with. (1) Identification of novel Zic-binding proteins, (2) The biological significance of the protein-to-protein interaction between Zic and Zic-binding proteins, (3) Post-translational modification of Zic proteins, (4) Bio-signals that have contact points with Zic proteins.Following points were revealed and publicized in the scientific community.(1) Identification of novel two Zic2-containing high-molecular-weight molecular complexes (Ishiguro et al.,2007). Identification of I-mfa as a Zic-repressor by yeast two-hybrid screening. (2,3) Identification of a Zic2-kinase in the HMW molecular complexes. The phosphorylation of Zic2 protein was shown to be critical in the transcriptional regulatory processes. Other modifications sites in Zic proteins have been identified and characterized by mass spectrometry analysis. (4) The Zic related bio-signals was investigated by analyzing the Zic1/3 and Zic2/3 compound mutant mice (Inoue et al., 2007a; 2007b). In particular, we revealed that Zic1 and Zic3 have critical roles in the expansion of forebrain neuronal precursors. Wnt signals was suggested to be involved in the Zic mediated developmental control. In addition, functional similarity and difference among vertebrates Zic genes have been investigated in mouse and Xenopus (Ishiguro et al.,2004; Fujimi et al.,2006).