Cell-Cell Adhesion During Nephron Development Is Driven by Wnt/PCP Formin Daam1

Abstract

E-cadherin junctions facilitate the assembly and disassembly of cell-cell contacts that drive development and homeostasis of epithelial tissues. The stability of E-cadherin-based junctions highly depends on their attachment to the actin cytoskeleton, but little is known about how the assembly of junctional actin filaments is regulated. Formins are a conserved group of proteins responsible for the formation and elongation of filamentous actin (F-actin). In this study, using Xenopus embryonic kidney and Madin-Darby canine kidney (MDCK) cells, we investigate the role of the Wnt/ planar cell polarity (PCP) formin protein Daam1 (Dishevelled-associated activator of morphogenesis 1) in regulating E-cadherin based intercellular adhesion. Using live imaging we show that Daam1 localizes to newly formed cell-cell contacts in the developing nephron. Furthermore, analyses of junctional F-actin upon Daam1 depletion indicate a decrease in microfilament localization and their slowed turnover. We also show that Daam1 is necessary for efficient and timely localization of junctional E-cadherin, which is mediated by Daam1′s formin homology domain 2 (FH2). Finally, we establish that Daam1 signaling is essential for promoting organized movement of renal cells. This study demonstrates that Daam1′s formin junctional activity is critical for epithelial tissue organization.

A comparative study of cellular diversity between the Xenopus pronephric and mouse metanephric nephron

“…Stages 12.5-20 provide a window to evaluate the initial inductive events that establish the kidney progenitors 43,61,62 . At stage 30, cellular movements and epithelization leads to the formation the epithelial tube 22,63 . By stage 37, the nephron begins to function, with specialized segments that reabsorb nutrients as fluid starts to flow through the kidney 22,64 .…”