rab11 is required for epithelial cell viability, terminal differentiation, and suppression of tumor-like growth in the drosophila egg chamberrab11上皮细胞生存能力,需要终端分化和抑制肿瘤生长的果蝇卵室.pdfVIP

Rab11 Is Required for Epithelial Cell Viability, Terminal Differentiation, and Suppression of Tumor-Like Growth in the Drosophila Egg Chamber Jiang Xu, Lan Lan, Nicholas Bogard, Cristin Mattione, Robert S. Cohen* Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas, United States of America Abstract Background: 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, have been well described and occur many times over in a single ovary. Methodology/Principal Findings: Here we 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. We 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. We also show that rab11-null FSCs give rise to normal numbers of cells that enter polar, stalk, and epithelial cell differentiation pathways, but that none of the cells complete their differentiation programs and that the epithelial cells undergo premature programmed cell death. Finally we show, through the induction of rab11-null clones at later points in the differentiation program, that Rab11 suppresses tumor-like growth of epithelial cells. 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 a