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The Rho guanine nucleotide exchange factor Trio is required for neural crest cell migration and interacts with Dishevelled

Item Type:Article
Title:The Rho guanine nucleotide exchange factor Trio is required for neural crest cell migration and interacts with Dishevelled
Creators Name:Kratzer, M.C. and Becker, S.F.S. and Grund, A. and Merks, A. and Harnoš, J. and Bryja, V. and Giehl, K. and Kashef, J. and Borchers, A.
Abstract:Directional migration during embryogenesis and tumor progression faces the challenge that numerous external signals need to converge to precisely control cell movement. The Rho guanine exchange factor (GEF) Trio is especially well suited to relay signals as it features distinct catalytic domains to activate Rho GTPases. Here we show that Trio is required for Xenopus cranial neural crest (NC) cell migration and cartilage formation. Trio cell-autonomously controls protrusion formation of NC cells and Trio morphant NC cells show a blebbing phenotype. Interestingly, the Trio GEF2 domain is sufficient to rescue protrusion formation and migration of Trio morphant NC cells. We show that this domain interacts with the DEP/C-terminus of Dishevelled (DVL). DVL - but not a deletion construct lacking the DEP domain – is able to rescue protrusion formation and migration of Trio morphant NC cells. This is likely mediated by activation of Rac1, as we find that DVL rescues Rac1 activity in Trio morphant embryos. Thus, our data provide evidence for a novel signaling pathway, whereby Trio controls protrusion formation of cranial NC cells by interacting with DVL to activate Rac1.
Keywords:GEF-Trio, Neural Crest Cell Migration, Dishevelled, Rho GTPases, Cadherin-11, Animals, Xenopus laevis
Source:Development
ISSN:0950-1991
Publisher:Company of Biologists
Volume:147
Number:10
Page Range:dev186338
Date:22 May 2020
Official Publication:https://doi.org/10.1242/dev.186338
PubMed:View item in PubMed

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