A NOVEL GENETIC APPROACH FOR ELUCIDATING GLYCOPEPTIDE HORMONE FUNCTIONS

这个子项目是众多研究子项目之一

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 signaling pathways play essential roles in female health and fertility and are critical for normal physiological control in mammals. Ligands for these receptors include the gonadotropins, FSH and LH, and the thyroid regulator TSH. Mutations that alter the activities of these ligands or their cognate receptors are associated with severe developmental defects, impaired fertility, and a wide range of health deficits. Although the cascade of intracellular signaling events that follows binding of the glycopeptide hormones to their cell surface receptors has been the subject of intensive investigations for many years, much remains unknown regarding the pathways? effectors, modulators, and targets. Strikingly, systematic functional and genetic analyses of glycopeptide hormone signaling have not yet been carried out in any model organism, despite the clear strengths of these systems in elucidating signal transduction networks. To gain insight into the developmental functions and regulatory mechanisms underlying glycopeptide hormone receptor signaling, we have undertaken studies of FSHR-1, the sole C. elegans ancestral ortholog of the FSH/LH/TSH receptor. Using a powerful genetic approach, we have identified 85 genes that act coordinately with FSHR-1 to control embryonic and larval development, germline sexual determination, germ cell maturation, and growth. Based on extensive precedent, we expect that many of these regulatory networks and biological functions will be conserved in higher organisms. Thorough knowledge of these pathways will be critical for understanding the complex effects of glycopeptide hormone signaling on human health, reproduction, and disease.