The long term goal of this work is to understand how cell division and differentiation are regulated in response to a combination of extracellular and intracellular signals. In humans improper control of cell division and/or differentiation may produce a variety of developmental abnormalities, including birth defects, cancer and autoimmune disease. The specific focus of this research is geared toward understanding how cell division and differentiation are regulated within the germline of the nematode, Caenorhabditis elegans. In the adult germline, mitoses are confined to the distal region of the gonad; germ cells that have progressed proximally from this region enter meiosis and initiate gametogenesis. Previous work has demonstrated that meiotic progression (specifically exit from pachytene) is dependent on several genes of the MAP kinase cascade (let-60 RAS, lin-45 RAF, mek-2 MAPKK and mpk-1 MAPK), each of which is also required for the induction of the hermaphrodite vulva. More recent data suggest that RAS-MAPK may also regulate distal proliferation and apoptosis within the germline.One of the goals of the work proposed here is to characterize a newly identified gene, pex-1 (pachytene exit), which is required for exit from pachytene, but not for vulval induction. Other mutations that specifically affect exit from pachytene will also be sought and characterized. In addition, a combination of genetic, molecular and cell biological methods will be directed toward determining how RAS is activated in the germline and identifying the targets of MAPK in the germline. Reverse genetic methods will be used to determine whether the regulation of pachytene exit within the nematode germline utilizes gene products homologous to those that control oocyte maturation in vertebrates.
