Multiple Distinct Roles for the Rab11 GTPase in the Somatic Cells of the Drosophila Egg Chamber

Abstract

The Drosophila egg chamber provides an excellent system in which to study the specification and differentiation of epithelial cell fates because all of the steps, starting with the division of the corresponding stem cells (called follicle stem cells or FSCs), have been well described and occur many times over in a single ovary. Here I investigate the role of the small Rab11 GTPase in follicle stem cells (FSCs) and in their differentiating daughters, which include main body epithelial cells, stalk cells and polar cells. I show that rab11-null FSCs maintain their ability to self renew, even though previous studies have shown that FSC self renewal is dependent on maintenance of E-cadherin-based intercellular junctions, which in many cell types, including Drosophila germline stem cells, requires Rab11. I also show that rab11-null FSCs give rise to cells that enter polar, stalk, and epithelial cell differentiation pathways, but that none of the cells are able to complete their differentiation programs and that the epithelial cells undergo premature programmed cell death. Finally I show, through the induction of rab11-null clones at later points in the differentiation program, that Rab11 suppresses tumor-like epithelial cell growth. Thus, rab11-null epithelial cells arrest differentiation early, assume an aberrant cell morphology, delaminate from the epithelium, and invade the neighboring germline cyst. These phenotypes are associated with defects in E-cadherin localization and a general loss of cell polarity. While previous studies have revealed tumor suppressor or tumor suppressor-like activity for regulators of endocytosis, this study is the first to identify such activity for regulators of endocytic recycling. This study also supports the recently emerging view that distinct mechanisms regulate junctional stability and plasticity in different tissues.