The adult C. elegans hermaphrodite gonad is organized along a distal to proximal axis. Mitosis occurs distally and is followed proximally by meiosis and gametogenesis. Mutations that cause a proximal proliferation (Pro) phenotype alter this pattern without affecting the ability of the cells to execute their normal fates (Schedl, 1997). Specifically, in addition to the normal distal-to-proximal pattern of "mitosis, meiosis, gametogenesis", a second cluster of mitotic germ cells is observed proximal to mature gametes. Identification and analysis of genes that, when mutant, cause this phenotype will reveal mechanisms by which the germline pattern is normally generated and maintained. As part of a genetic screen to identify loci involved in germline development, we identified three temperature sensitive Pro mutants that proved to be new
glp-1 alleles. Activity of the well-characterized GLP-1 receptor, a member of the LIN-12/Notch family, is associated with maintenance of mitosis and/or inhibition of meiosis in the germ line (Austin and Kimble, 1987; Schedl, 1997). The distal germ line remains mitotic due to GLP-1-mediated signaling from the distal tip cell (DTC) to the distal germ line (Austin and Kimble, 1987). The current understanding for spatial control of meiotic entry in the L3 is that as the germ line grows, cells in the proximal germ line enter meiosis by default as their distance from the DTC increases. Our
glp-1(Pro) alleles offer additional insight into mechanisms regulating the spatial control of L3 meiotic entry. To distinguish between several possible models for the cellular origin of the
glp-1(Pro) phenotype, we performed a detailed time-course analysis. In the wild-type L3, the proximal-most germ cells are the first cells to enter meiosis. In
glp-1(Pro) mutants, however, the proximal-most germ cells do not enter meiosis whereas more distally-located cells adopt the appropriate distal-to-proximal pattern. Therefore, our data suggest that perhaps two mechanisms exist in the wild type, one proximal and one distal, that act in concert to restrict meiotic entry to the proximal-most region of the L3 germ line. On-going genetic and phenotypic analysis is aimed at determining the precise nature of these alleles and their dependence on ligands and effectors in the LIN-12/Notch signaling pathway.