Integrins positively regulate cell survival in the wing imaginal disc in Drosophila melanogaster

Abstract

Integrins are a widely expressed family of transmembrane receptors that binds preferentially extracellular matrix components. Integrins can provide mechanical links and activate different pathways, thus regulating various cellular processes, including cell survival. In fact, disruption of integrin function results in a class of apoptosis called anoikis. Although there is a lot of information about the role of integrins in promoting cell survival in cell culture experiments, little is known about its role during morphogenesis. In this study we aim to better understand the role of integrins in regulating cell survival during development using Drosophila wing imaginal disc as a model system. We show that loss of integrin function in the wing disc results in caspase dependent anoikis and cell extrusion. Removal of integrins results in ectopic activation of JNK pathway, which in turn leads to an increase in the expression of the proapoptotic gene hid. These results suggest that integrins regulate cell survival by inhibiting hid expression through downregulation of JNK pathway. In addition, loss of integrin function results in an increase in myosin tension which per se has shown to induce cell death and extrusion. Moreover, blocking cell death in a lack of integrin function context does not prevent cell extrussion. Given these results we would like to propose that elimination of integrin function results in an increase in tension and cellular extrusion that precludes cell death. Thus, in a physiological context integrins would act as mechanosensors and could regulate cell survival in part by controlling cellular tension.