Cling film – a novel regulator of epithelial morphogenesis
Authors: Clara-Maria Ell 1,2,3; George Pyrowolakis 2,3
Affiliations: 1) Spemann Graduate School of Biology and Medicine (SGBM), Albert-Ludwigs University of Freiburg, Germany; 2) CIBSS - Centre for Integrative Biological Signalling Studies, Albert-Ludwigs University of Freiburg, Germany; 3) Faculty of Biology, Institute for Biology I, Albert-Ludwigs University of Freiburg, Germany
Keywords: o. tissue growth and remodeling; s. extracellular matrix
Epithelial morphogenesis is essential for the transformation of simple epithelial sheets into complex organs. The Drosophila larval wing undergoes drastic changes during pupal development and has served as a valuable model to address the underlying mechanisms at tissue-, cell- and subcellular-level. Changes include proliferation, cell rearrangements, cell shape modulation and drastic extracellular matrix (ECM) remodeling, all of which are tightly regulated by intrinsic and extrinsic cues and forces. Here we describe Cling film (Cling), a target of patterning cues in larval wing discs, as a novel regulator of wing morphogenesis. Cling encodes a transmembrane protein with a large, multi-domain extracellular region which predominantly localizes to the apical cell surface. Expression of cling starts in a spatially defined pattern in late larval wing discs and becomes more uniform in the early pupal stages. Adult wings of cling mutants are severely malformed and strongly folded. We could show that defects in cling mutants manifest in early pupal stages and that cling mutant pupal wings increase their surface normally but fail to stretch out along the proximo-distal axis resulting in heavily folded wings. The phenotype is accompanied by failure to degrade the apical ECM, while genetic ablation of the apical ECM component Dumpy can fully restore wing expansion in cling mutants. Our results indicate that Cling is critically involved in patterned ECM remodeling during early wing morphogenesis. We are currently investigating interactions of Cling with structural ECM components and the ECM degrading proteases Stubble and Notopleural.