Modulation of integrin levels triggers actomyosin reorganization essential for proper tissue folding
Authors: Andrea Valencia Expósito 1; Nargess Khalilgharibi 2; Yanlan Mao 2; María Dolores Matín Bermudo 1
Affiliations: 1) Centro Andaluz de Biología del Desarrollo, CSIC/Universidad Pablo de Olavide/JA, Sevilla, Spain; 2) MRC Laboratory for Molecular Cell Biology, University College London, London, UK
Keywords: g. wing disc; t. cell junctions and adhesion
Folding of epithelial tissues is essential for the formation of complex three-dimensional organ structures during development. However, while folding of epithelial tissues towards the apical surface has been long studied, little is known about the mechanisms underlying epithelial folding towards the basal side. Both apical and basal epithelial tissue folding are accompanied by changes in actomyosin organization and in cell adhesion. Manipulation of apical adhesion molecules, such as cadherins, affects actomyosin dynamics and apical folding. Similarly, adhesion of the cells to the basement membrane (BM), via integrins, is required for proper basal epithelia folding. Nevertheless, how changes in cell adhesion and actomyosin organization interact with each other to drive epithelial folding during morphogenesis remains unknown. Here, we use the primordium of the wing, the Drosophila wing imaginal disc epithelium, as a model system to analyse the role of integrins on the regulation of the actomyosin rearrangements and cell shape changes underlying basal tissue folding. The wing imaginal disc is an epithelial sac contacting on its basal side with a BM. During its development, the disc folds basally along a row of cells, the future wing margin cells. In this work, we show that basal disc folding involves four interconnected events: reduction on integrin levels, increase of F-actin accumulation basolaterally, cell shortening and detachment from the BM. We show that ectopic maintenance of high levels of integrins in wing margin cells prevents these changes, leading to abnormal folding of the epithelium. Contrariwise, reduction of integrin levels in an ectopic location in the disc recapitulates the events that take place at the wing margin, resulting in the formation of an ectopic fold. Finally, through computational exploration, we have found that the reduction of adhesion to the BM must preceed the changes in F-actin reorganization and cell shortening to allow proper folding of the epithelium. Based on these results, we propose that changes in the adhesion of cells to the BM mediated by integrins trigger modifications in the actomyosin network necessary for basal epithelial folding during organogenesis.