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Development. 2018 Feb 2. pii: dev.157495. doi: 10.1242/dev.157495. [Epub ahead of print]

The elmo-mbc complex and rhogap19d couple Rho family GTPases during mesenchymal-to-epithelial-like transitions.

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Aix-Marseille Univ, CNRS, IBDM, Case 907, 13288 Marseille, Cedex 09, France
Aix-Marseille Univ, CNRS, IBDM, Case 907, 13288 Marseille, Cedex 09, France.


Many metazoan developmental processes require cells to transition between migratory mesenchymal- and adherent epithelial-like states. These transitions require Rho GTPase-mediated actin rearrangements downstream of integrin and cadherin pathways. A regulatory toolbox of GEF and GAP proteins precisely coordinates Rho protein activities, yet defining the involvement of specific regulators within a cellular context remains a challenge due to overlapping and coupled activities. Here we demonstrate that Drosophila dorsal closure is a powerful model for Rho GTPase regulation during transitions from leading edges to cadherin contacts. During these transitions a Rac GEF elmo-mbc complex regulates both lamellipodia and Rho1-dependent, actomyosin-mediated tension at initial cadherin contacts. Moreover, the Rho GAP Rhogap19d controls Rac and Rho GTPases during the same processes and genetically regulates the elmo-mbc complex. This study presents a fresh framework to understand the inter-relationship between GEF and GAP proteins that tether Rac and Rho cycles during developmental processes.


Cadherin; Cell-cell contact; Elmo-Dock; Leading edge; Rho signaling; arhgap21


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