Cell Non-autonomous Function of daf-18/PTEN in the Somatic Gonad Coordinates Somatic Gonad and Germline Development in C. elegans Dauer Larvae

Abstract

C. elegans larvae integrate environmental information and developmental decisions [1-3]. In favorable conditions, worms develop rapidly and continuously through four larval stages into reproductive adulthood. However, if conditions are unfavorable through the second larval stage, worms enter dauer diapause, a state of global and reversible developmental arrest in which precursor cells remain quiescent and preserve developmental potential, anticipating developmental progression if conditions improve. Signaling from neurons, hypodermis, and intestine regulate the appearance and behavior of dauer larvae and many aspects of developmental arrest of the non-gonadal soma [1, 4, 5]. Here, we show that the decision of somatic gonad blast cells (SGBs) and germline stem cells (GSCs) to be quiescent or progress developmentally is regulated differently from the non-gonadal soma: daf-18/PTEN acts non-autonomously within the somatic gonad to maintain developmental quiescence of both SGBs and GSCs. Our analysis suggests that daf-18 acts in somatic gonad cells to produce a "pro-quiescence" signal (or signals) that acts inter se and between the somatic gonad and the germline. The inferred signal does not require DAF-2/insulinreceptor or maintain quiescence of the nearby sex myoblasts, and developmental progression in daf-18(0) does not require dafachronic acids. Abrogating quiescence in dauer results in post-dauer sterility. Our results implicate the somatic gonad as an endocrine organ to synchronize somatic gonad and germline development during dauer diapause and recovery, and our finding that PTEN acts non-autonomously to control blast cell quiescence may be relevant to its function as a tumor suppressor in mammals and to combating parasitic nematodes.