daf-18/PTEN function in the germline of c.elegans

C.elegans germ line is an excellent model system for studying the molecular controls of stem cells  proliferation and differentiation. Germline stem cells reside at the distal part of the gonad and divide continuously during development. As development proceeds,germcells located far from the distal part enter meiosis and then differentiate in to sperm (during L4) or oocytes (during adulthood). In the distal part of the gonad, germline stem cells are maintained by GLP-1/Notch signal and FBF proteins. gld genes that act downstream of GLP-1/Notch pathway are required to inhibit proliferation and/or promote meiotic entry. The insulin/IGF-like receptor daf-2 is well known for its roles in the dauer decision and aging. Recently it has been shown that C.elegens germline regulates its lifespan and mutations in daf-2 reduce germline tumors caused by gld-1 inactivation. These observations give a hint about possible interaction between Notch and Insulin like signaling pathways. However till to date, no interaction has been reported between these two pathways in C.elegans. PTEN is a well-characterized tumor suppressor in mammals and is antagonize Insulin pathway. In C.elegans daf-18/PTEN was well studied for a role in lifespan regulation but its tumor suppressor roles has not been characterized due to redundancy. Aim of my present work is to study daf-18/PTEN role in germline development and its interaction with Notch signaling pathway. For this we are studying genetic interaction between daf-18 and other genes in the notch pathway. We will also study molecular interaction between daf-18 and notch pathway to test whether notch regulates daf-18 gene expression. To get further insight in cross talk between Insulin-like/PI3K and Notch pathways we will extend genetic interaction studies for other genes in both pathways.