Elucidation of the mechanism of sex differentiation and its application to effective reproduction of animal resources

本研究旨在阐明性腺性别分化的机制，并将其应用于动物资源的有效繁殖，主要分析了与性腺发育有关的转录因子的功能和表达，此外，从哺乳动物物种延伸到其他动物的分析帮助我们阐明了脊椎动物共同的机制以及动物物种的特异性。Nagahama博士从青鳉鱼中克隆了编码Ad 4 BP/SF-1的基因，通过使用这些DNA，对Ad 4 BP/SF-1和Dax-1基因表达的调节进行了广泛的努力。结果表明，Dax-1基因受Ad 4 BP/SF-1功能的正调节，Ad 4 BP/SF-1是一种重要的基因调控因子，在性腺发育过程中起着重要的调控作用，同时，我们还对Ad 4 BP/SF-1从肾上腺-性腺原基到肾上腺或性腺原基的发育过程进行了分析，结果表明，Ad 4 BP/SF-1是哺乳动物性腺分化所必需的转录因子，虽然性别分化的精细机制仍有待阐明，但本研究为进一步研究提供了重要线索。

The present research was performed to elucidate a mechanism underlying sex differentiation of the gonads and to apply it to effective reproduction of animal resources.Functions and expressions of transcription factors implicated in the gonadal development were mainly analyzed.In addition, analyses extending to other animals from mammalian species helped us to clarified the mechanism common to vertebrate as well as specific for animal species.Actually cDNAs and genes encoding Ad4BP/SF-1 were cloned from Medaka (fish) by Dr.Nagahama, from a frog (amphibian) by Dr.Nakamura, and from a chicken (bird) by Dr.Kudo.By using these DNAs, extensive efforts were made to elucidate the regulation of the Ad4BP/SF-1 and Dax-1 gene expression.As the results, it was clarified that the Dax-1 gene is positively regulated by the function of Ad4BP/SF-1, which probably constitutes a cascade of gene regulation functioning in the gonadal development.Analyses were also performed during the developmental process from an adreno-gonadal primordium to either an adrenal or gonadal primordium.Based on these observations, it was strongly suggested that Ad4BP/SF-1, originally identified as the transcription factor essential for differentiation of the mammalian gonads, play similar roles among other animal species.Although the fine mechanism of the sex differentiation has remained to be elucidated, the present study gives important cues for further investigation.