Cadherin switching during the formation and differentiation of the Drosophila mesoderm – implications for epithelial-to-mesenchymal transitions

Abstract

BSTRACTEpithelial-to-mesenchymal transition (EMT) is typically accompanied by downregulation of epithelial (E-) cadherin, and is often additionally accompanied by upregulation of a mesenchymal or neuronal (N-) cadherin. Snail represses transcription of the E-cadherin gene both during normal development and during tumour spreading. The formation of the mesodermal germ layer in Drosophila, considered a paradigm of a developmental EMT, is associated with Snailmediated repression of E-cadherin and the upregulation of Ncadherin. By using genetic manipulation 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. However, we discover different effects of E-and N-cadherin on the differentiation of subsets of mesodermal derivatives, which depend on Wingless signalling from the ectoderm, indicating differing abilities of E-and Ncadherin to bind to and sequester the common junctional and signalling effector b-catenin. These results suggest that the downregulation of E-cadherin in the mesoderm might be required to facilitate optimal levels of Wingless signalling.

Wnt3a expression is associated with epithelial-mesenchymal transition and promotes colon cancer progression

“…The nuclear translocation of β-catenin leads to the breakdown of cell-to-cell adhesion formed by β-catenin and E-cadherin. This phenomenon has been extensively studied in both morphological and biochemical EMT processes regardless of inducers and origins [35]. Our results showed that ectopic Wnt3a expression in HCT116 increased the expression and intracellular distribution of β-catenin and of the wellestablished target proteins of Wnt/β-catenin signaling, namely, c-myc, and cyclin D1.…”

Epithelial‐mesenchymal Transition and Cancer Stem Cells: At the Crossroads of Differentiation and Dedifferentiation

“…The expression of N-cadherin plays roles in differentiation: For example, N-cadherin expression controls myogenic differentiation (Charrasse et al, 2002). Recently, Schafer et al suggested that, in addition to the surface adhesion changes caused by the cadherin switch, Snail may serve to facilitate downstream events such as Wnt signaling (Schäfer et al, 2014). The Wnt signaling pathway is well known to participate in cell proliferation and cell differentiation (Reya and Clevers, 2005).…”

A common framework for EMT and collective cell migration

“…This reduction in intercellular adhesion is achieved largely by sequential changes in cadherin expression and is known as the 'cadherin switch' (Taneyhill, 2008). However, the functional relevance of the switch from E-cadherin transcription in epithelial cells to N-cadherin transcription as they transit to mesenchymal cells during EMT in organisms such as frog, chick and fly (Hatta and Takeichi, 1986;Nandadasa et al, 2009;Oda et al, 1998) is currently under question, as it has been elegantly proven that it is not required for the segregation or dispersal of the mesodermal germ layer in Drosophila (Schafer et al, 2014). Thus, similar to E-cadherin transcriptional repression, it is likely that in some systems a 'cadherin switch' is also dispensable for EMT.…”