Hong, S.K., Haldin, C.E., Lawson, N.D., Weinstein, B.M., Dawid, I.B., and Hukriede, N.A. (2005) The zebrafish kohtalo/trap230 gene is required for the development of the brain, neural crest, and pronephric kidney. Proc Natl Acad Sci U S A 102(51): 18473-18478.
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.