The zebrafish kohtalo/trap230 gene is required for the development of the brain, neural crest, and pronephric kidney

Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 01/2006; 102(51):18473-8. DOI: 10.1073/pnas.0509457102
Source: PubMed


Mutation of the gene encoding the Mediator component thyroid hormone receptor-associated protein (TRAP)230/MED12 affects the development of multiple systems in zebrafish embryogenesis. We isolated two ethylnitrosourea-induced alleles in the gene encoding this protein and named the locus kohtalo (kto) after the homologous locus in Drosophila. Homozygous kto mutant zebrafish embryos show defects in brain, neural crest, and kidney development and die at approximately 6 days postfertilization. In the affected tissues, differentiation is initiated and many cell type-specific genes are expressed, but there is a failure of morphogenesis and failure to complete differentiation. These results suggest that critical targets of TRAP230 function may include proteins important for cell mobility, cell sorting, and tissue assembly.

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    • "In addition to CDK8 and CCNC, MED12 and MED13 are also critical regulators of developmental gene expression programs (Hong et al., 2005; Kennison & Tamkun, 1988; Rau et al., 2006; Wang et al., 2006). In a C. elegans RNAi screen, Med12 (dpy-22) was identified by the Fraser lab as a highly connected ''hub'' gene that regulated numerous signaling pathways (Lehner et al., 2006). "
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    • "Not surprisingly, the sox9a/sox9b double mutant displayed severe craniofacial abnormalities. Zebrafish mutants in Trap230/Med12, a transcriptional co-activator for Sox9, were characterized by disrupted cartilage development [40], [41]. Furthermore, knockdown experiments showed that runx2b and runx3 are critically involved in chondrogenesis: runx2b morphants lack the entire pharyngeal skeleton whereas only rudimentary trabeculae are formed in runx3 morphants [42]. "
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    • "Notably, MED12 is required for normal neuronal development in zebrafish, most likely by acting as a coactivator of the transcription factor Sox9; as in our study, some, but not all neurons were affected by med12 mutations (Hong et al., 2005; Wang et al., 2006). In Drosophila cdk8 mutants were isolated in genetic screens for wiring defects in the visual system (Berger et al., 2008). "
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