Molecular Mechanisms of Gonadal Sex Differentiation

点击翻译按钮获取中文摘要

Gonad is the tissue showing the most prominent sexual difference. Moreover, the gonad induces sex differentiation of other tissues through production of sex steroid hormones. The following studies were performed to elucidate the molecular mechanisms underlying gonad sex differentiation.(1)Vinexine was isolated as a protein interacting with Ad4BP/SF-1. Since the expression was detected in the developing fetal gonads, the gene KO mouse was generated and the phenotype was examined. Interestingly, the KO mouse showed XY sex reversal and phosphorylation of ERK was reduced significantly in the male fetal gonad.(2)Functions of a homeo box protein, Arx, were examined with the gene KO mouse, and found that Arx is involved in Leydig cell differentiation. Moreover, the gene mutation was found to cause a human disease, X-linked lissencephaly with abnormal genitalia.(3)With respect to posttranslational modification of Ad4BP/SF-1, we revealed that Ad4BP/SF-1 is SUMOylated and phosphorylated. SUMOylation suppressed transcriptional activity. Interestingly, Sox9 was also SUMOylated and the SUMOylation of these two transcription factors suppressed their synergistic transcription of the MIS gene. The effects of phosphorylation is still under investigation.