Daf-18/PTEN is locally rescued to couple germline stem cell proliferation to oocyte accumulation in C. elegans

Jichao Deng¹, Patrick Narbonne¹

¹Département de Biologie Médicale, Université du Québec à Trois-Rivières, Trois-Rivières, Québec, Canada.

Cowden syndrome is an autosomal dominantgenetic disease caused by a germline mutation of PTEN/DAF-18, and it is characterized bythe development of benign tumors across the whole body, and an overall increased chance to develop cancer. The precise molecular mechanisms that lead to tumors formation however remain unclear. In feminized C. elegans daf-18 hermaprhodites, benign tumors develop and consist of properly differentiated oocytes that keep accumulating owing to a defect in homeostatic germline stem cell regulation. Here, we traced back the origin of the germline tumors to a miscommunication between the differentiated stem cell progeny (the oocytes) and their parental stem cells. Our data suggest that daf-18 acts to inhibit ERK/MAPK signaling to induce germline stem cell (GSC) quiescence during homeostatic signaling, but we do not know the tissue in which this takes place. To identify this tissue, we rescued daf-18 in the gut, neurons, hypodermis and muscles of daf-18 null mutants. Furthermore, given the role of autophagy in the control of germline proliferation, and that daf-18 has been reported to function in the bec-1/daf-2/skn-1 pathway, we are testing whether daf-18 may inhibit skn-1 signaling to control oocytes accumulation and GSC proliferation. Therefore, our study will identify where daf-18 activity is required to prevent germline tumor formation, and whether it does so though regulating the autophagy pathway.