BMPシグナル伝達系の下流転写因子SEF1/SIP-1ファミリーの研究

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SIP1, a transcription factor belonging to δEF1/zfh (zinc-finger and homeodomain) family, can interact with the Smad proteins in a TGFβ-dependent manner. To elucidate the role of SIP1 in mouse development, we examined its expression during embryogenesis, and generated the SIP1 KO mouse.At E7.5, SIP1 is widely expressed in mesoderm except for the node and notochord. At E8.5, specific expression is observed in the neural tube and presomitic mesoderm. At later developmental stages, it is expressed in lens epithelium, neural crest derivatives, and dermamyotome. For targeting the SIP1 gene, exon 7 was deleted to truncate most and functional part of the SIP1 protein. Homozygous mutants begin to exhibit abnormal development around E8.25. Notochord and somites appear to be severely affected and not properly formed. The mutant embryos also display defects in neural tube closure, and fail to turn. We will investtigate the role of SIP1 in the notochord, somite, and neural tube formation.