ANALYSIS OF THE MULTIPLE ROLES OF GLD-1 IN GERMLINE DEVELOPMENT - INTERACTIONS WITH THE SEX DETERMINATION CASCADE AND THE GLP-1 SIGNALING PATHWAY

The Caenorhabditis elegans gene gld-1 is essential for oocyte developm ent; in gld-1(null) hermaphrodites, a tumor forms where oogenesis woul d normally occur. We use genetic epistasis analysis to demonstrate tha t tumor formation is dependent on the sexual fate of the germline. Whe n the germline sex determination pathway is set in the female mode (te rminal fem/fog genes inactive), gld-1(null) germ cells exit meiotic pr ophase and proliferate to form a tumor, but when the pathway is set in the male mode, they develop into sperm. We conclude that the gld-1(nu ll) phenotype is cell-type specific and that gld-1(+) acts at the end of the cascade to direct oogenesis. We also use cell ablation and epis tasis analysis to examine the dependence of tumor formation on the glp -1 signaling pathway. Although glp-1 activity promotes tumor growth, i t is not essential for tumor formation by gld-1(null) germ cells. Thes e data also reveal that gld-1(+) plays a nonessential (and sex nonspec ific) role in regulating germ cell proliferation before their entry in to meiosis. Thus gld-1(+) may negatively regulate proliferation at two distinct points in germ cell development: before entry into meiotic p rophase in both sexes (nonessential premeiotic gld-1 function) and dur ing meiotic prophase when the sex determination pathway is set in the female mode (essential meiotic gld-1 function).