Cadherin switching during the formation and differentiation of the Drosophila mesoderm: implications for epithelial mesenchymal transitions

Abstract

Epithelial-to-mesenchymal transitions (EMT) are typically accompanied by downregulation of epithelial (E-) cadherin, and often additionally by upregulation of a mesenchymal/neuronal (N-) cadherin. Snail represses transcription of the E-cadherin gene both during normal development and during tumor spreading. The formation of the mesodermal germ layer in Drosophila, considered a paradigm of a developmental EMT, is associated with Snail-mediated repression of E-cadherin and the upregulation of N-cadherin. Using genetic manipulations to remove or overexpress the cadherins, we show here that the complementarity of cadherin expression is not necessary for the segregation or the dispersal of the mesodermal germ layer in Drosophila. We however discover differential effects on E- and N-cadherin on the differentiation of subsets of mesodermal derivatives, which depend on Wingless signalling from the ectoderm, indicating differential abilities of E- and N-cadherin to bind and sequester the common junctional and signalling effector beta-catenin. They suggest that the need to downregulate E-cadherin in the mesoderm may be to facilitate optimal levels of Wingless signalling.