Integrins control tissue morphogenesis and homeostasis by sustaining the different types of intracellular actin networks

Abstract

29Forces generated by the actomyosin cytoskeleton are key contributors to the 30 generation of tissue shape. Within the cell, the actomyosin cytoskeleton organizes in 31 different types of networks, each of them performing distinct roles. In addition, 32 although they normally localize to precise regions of the cells, they are rarely 33 independent and often their dynamics influence each other. In fact, the reorganization of 34 a given structure can promote the formation of another, conversions that govern many 35 morphogenetic processes. In addition, maintenance of a specific actomyosin network 36 organization in a differentiated tissue might be equally important. Failure to do so could 37 lead to undesired cell state transitions, which in turn would have drastic consequences 38 on the homeostasis of the tissue. Still, little is known about the mechanisms that ensure 39 controlled transitions between actomyosin networks during morphogenesis or their 40 maintenance in a differentiated tissue. Here, we use the Drosophila follicular epithelium 41 to show that cell-ECM interactions mediated by integrins are necessary for the 42 establishment and maintenance of the different actomyosin networks present in these 43 epithelial cells. Elimination of integrins in a group of follicle cells results in changes in 44 the F-actin levels and physical properties of their intracellular actomyosin networks. 45Integrin mutant follicle cells have reduced number of basal stress fibers. They also show 46 increased cortical F-actin levels and tension, which interferes with proper basal surface 47 growth. Finally, clonal elimination of integrins also triggers non-autonomous 48 behavioural changes in neighbouring wild types cells, which now reorganize their actin 49 cytoskeleton and spread and overlay the mutant ones. Based on these results, we 50propose that cell-ECM interactions mediated by integrins regulate epithelia 51 morphogenesis and homesostasis by preserving the different types of intracellular actin 52 networks. 53 54 55 56 57 58 59 60 61 62 Forces generated by F-actin networks are important contributors to the generation of 64 cell and tissue shape. The architecture and mechanical properties of the F-actin network 65 are modulated by myosin II motors and actin binding proteins (reviewed in 1 . The 66 molecular composition of contractile actin networks and bundles is highly conserved 67 among eukaryotic species 2 . Nevertheless, their organization and dynamics change 68 across different cell types, their position within the cell and the differentiation state of 69 the cell. 70 There are two main ways in which actomyosin networks can be organized within 71 the cell, as cortical two-dimensional meshworks below the plasma membrane or as 72 stress-fibers. Studies over the last decade have assigned distinct roles for these two 73 types of networks. Thus, while pulsatile contraction of cortical actomyosin meshworks 74 has been mainly implicated in the cell shape changes underlying key morphogenetic 75 processes, such as gastrulatio...