A NOVEL GENETIC APPROACH FOR ELUCIDATING GLYCOPEPTIDE HORMONE FUNCTIONS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 糖肽激素(GPH)信号通路在人类的健康和发育中起着至关重要的作用，对正常的生理控制和生育至关重要。为了更好地了解这些途径的发育功能，并在分子水平上揭示调节它们的信号转导的因素，我们对模式生物秀丽线虫进行了研究。我们的研究揭示了线虫GPH样受体FSHR-1在调节卵母细胞和精子发育、促进维持强大的生殖系干细胞种群以及通过抑制凋亡控制生殖细胞存活方面的作用。因此，我们的结果表明，GPH家族受体在控制生殖系发育和生育方面具有跨物种的保守作用。我们的数据还提出了一种模型，在该模型中，FSHR-1信号与已知的线虫性别决定途径通过胞体平行作用，控制生殖系发育的多个方面。更多的研究将进一步揭示线虫中GPH受体介导的信号的分子细节，这基于观察到的家族成员的功能保守，可能为人类如何调控这些重要的信号通路提供新的见解。

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. The glycopeptide hormone (GPH) signaling pathways play essential roles in human health and development and are critical for normal physiological control and fertility. To gain a better understanding of the developmental functions of these pathways as well as to uncover the factors that modulate their signaling at the molecular level, we have undertaken studies in the model organism, C. elegans. Our studies have revealed roles for the C. elegans GPH-like receptor, FSHR-1, in regulating oocyte and sperm development, in promoting the maintenance of a robust germline stem cell population, and in controlling germ cell survival by inhibiting apoptosis. Our results therefore indicate a conserved role for GPH family receptors across species in controlling germline development and fertility. Our data also suggest a model whereby FSHR-1 signaling acts in parallel to the known sex determination pathway of C. elegans, via the soma, to control multiple aspects of germline development. Additional studies will shed further light on the molecular details of GPH receptor-mediated signaling in C. elegans, which based on the observed functional conservation of family members, is likely to provide novel insight into how these important signaling pathways are regulated in humans.