Role of cofilin/twinstar in epithelial integrity and tissue growth in drosophila model organism

Abstract

Regulation of actin assembly and depolymerization is important for the organization of epithelia. Recent studies have shown that the actin capping proteins are required to prevent cell extrusion and inappropriate activation of Yorkie (Yki) activity in Drosophila, implicating the importance of actin regulation for epithelial integrity and Yki-dependent tissue growth. However, the role of Twin star (Tsr), the Drosophila homolog for Cofilin/Actin Depolymerization Factor (ADF), in epithelial integrity and Hpo signaling is unknown. Here I demonstrate that reduction of Tsr by RNAi or mutant clones in wing imaginal disc induces not only F-actin accumulation but also ectopic expression of Yki and its transcriptional target gene expanded (ex). Consistent with Yki activation, reduced Tsr resulted in increased DNA synthesis detected by BrdU labelling. Reduced Tsr also led to downregulation of cell junction proteins and extrusion of affected cells from the basal part of the epithelium. Further, Rho GTPase 1 (Rho1) was upregulated in Tsr-depleted tissue, supporting the Tsr function in the inhibition of cell migration. Tsr is also required for blocking cell death and JNK signaling. Thus, reduced Tsr affects wing disc by cell death-dependent and -independent ways. Remarkably, the invasiveness of Tsr-depleted cells is enhanced by inhibiting cell death. Taken together, my data suggest that Tsr is required for the suppression of Yki signaling for cell proliferation and for the maintenance of epithelial integrity. This study provides an insight into potential roles of ADF/Cofilin in invasive cell migration and tumor suppression in higher animals.