THE ROLE OF TFII-I TRANSCRIPTION FACTOR IN THE NEURAL TUBE CLOSURE DEFECTS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Neural tube closure defects (NTDs), in particular anencephaly and spina bifida, are common human birth defects. Risk of NTDs is inherited in humans, but usually not as a single dominant or recessive gene. The incidence of NTDs varies with ethnic group, socioeconomic group and time, but remains on the order of 1 in 1,000 births, despite the use of folate supplementation in early pregnancy. Thus, the use of mouse mutants and strains implicated in phenotype causation is very critical in our understanding of NTDs. TFII-I is a transcription factor with multiple helix-loop-helix repeat domains. The TFII-I knockout mice generated in our laboratory display several phenotypic manifestations including NTDs. In an effort to establish the molecular basis of NTDs, we will search for the downstream target genes regulated by the TFII-I family of transcription factors. We believe that certain set of genes in this category may be profoundly deregulated in the neural tube closure and are therefore most probably the immediate causal factors in NTDs. The establishment of the developmental genetic basis of NTDs is important beyond the understanding it brings to neural tube closure itself. The identification of genes that regulate neural tube development allows further investigation of genetic interactions that may be causal to NTD conditions.