Germ cell maintenance and differentiation are essential for fertility and reproduction. The mechanisms controlling both processes are interlinked and highly complex. Recently, we identified the Adhesion G protein-coupled receptor LAT-1 to have a function in the reproduction of C. elegans. A
lat-1 null mutant displays a reduced number of laid eggs and an increase in unfertilised oocytes. Phenotypic analyses showed that these defects are caused in parts by faulty sperm guidance, but also by alterations in oocyte maturation. Most prominently,
lat-1 mutant gonads displayed an elevated number of proliferating cells in the mitotic zone. Consistently, we observed a shift in the expression of the cell fate regulator
gld-1 to more proximal germ cell rows. Interestingly, comprehensive analyses of germline characteristics also revealed changes in the cell cycle in
lat-1 mutants. As one key regulator of germ cell proliferation versus differentiation is the Notch pathway, we investigated potential involvement of LAT-1 in Notch signaling. Epistasis and expression analyses suggest that LAT-1 cross-talks with the Notch pathway, but this seems to be independent of the Notch ligand LAG-2. This effect of LAT-1 is cell non-autonomous as the receptor is not present in germ cells but in cells of the somatic gonad such as the distal tip cell and gonadal sheath cells. Consistent with this notion, expressing the receptor specifically in the distal tip cell of nematodes with a
lat-1 null background rescues the altered number of mitoses. Interestingly, LAT-1 exerts its role from the distal tip cell not in a classical way via G protein signals as only the extracellular N terminus of the receptor is sufficient for LAT-1 function, thus indicating a unique signalling mechanism. In conclusion, we present the Adhesion GPCR LAT-1 as a new player in controlling germ cell proliferation and interfering with the Notch pathway. Thereby, it acts cell non-autonomously by an atypical signalling mechanism not involving G proteins.