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

SIP 1是一种属于锌指结构域（zinc-finger and homeodomain，δ EF 1/zfh）家族的转录因子，能以TGFβ依赖的方式与Smad蛋白相互作用。为了阐明SIP 1在小鼠发育中的作用，我们检测了SIP 1在胚胎发育过程中的表达，并建立了SIP 1基因敲除小鼠模型。在E8.5，在神经管和前体中胚层中观察到特异性表达。在发育后期，它在透镜上皮、神经嵴衍生物和真皮肌节中表达。为了靶向SIP 1基因，缺失外显子7以截短SIP 1蛋白的大部分和功能部分。纯合突变体开始在E8.25左右表现出异常发育。脊索和体节似乎受到严重影响，不能正常形成。突变的胚胎也显示出神经管闭合的缺陷，并且不能转动。我们将研究SIP 1在脊索、体节和神经管形成中的作用。

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.