The Dlg Module and Clathrin-Mediated Endocytosis Regulate EGFR Signaling and Cyst Cell-Germline Coordination in the Drosophila Testis

Abstract

Summary: Tissue homeostasis and repair relies on proper communication of stem cells and their differentiating daughters with the local tissue microenvironment. In the Drosophila male germline adult stem cell lineage, germ cells proliferate and progressively differentiate enclosed in supportive somatic cyst cells, forming a small organoid, the functional unit of differentiation. Here we show that cell polarity and vesicle trafficking influence signal transduction in cyst cells, with profound effects on the germ cells they enclose. Our data suggest that the cortical components Dlg, Scrib, Lgl and the clathrin-mediated endocytic (CME) machinery downregulate epidermal growth factor receptor (EGFR) signaling. Knockdown of dlg, scrib, lgl, or CME components in cyst cells resulted in germ cell death, similar to increased signal transduction via the EGFR, while lowering EGFR or downstream signaling components rescued the defects. This work provides insights into how cell polarity and endocytosis cooperate to regulate signal transduction and sculpt developing tissues. : In this article, Papagiannouli and colleagues show that Dlg, Scrib, Lgl, and clathrin-mediated endocytosis downregulate EGFR signaling levels in the somatic cyst cells of the Drosophila testis. Knockdown of their function in cyst cells results in cell non-autonomous apoptosis of the neighboring germline and increased levels of the EGFR downstream effector MAPK, mediated in part by the membrane phospholipid PIP2. Keywords: Drosophila spermatogenesis, dlg, scrib, lgl, endocytosis, polarity, EGFR regulation, clathrin, PIP2, septate junctions