Directional migration of neural crest cells in vivo is regulated by Syndecan-4/Rac1 and non-canonical Wnt signaling/RhoA

Citations Over TimeTop 10% of 2008 papers

Abstract

Directed cell migration is crucial for development, but most of our current knowledge is derived from in vitro studies. We analyzed how neural crest (NC) cells migrate in the direction of their target during embryonic development. We show that the proteoglycan Syndecan-4 (Syn4) is expressed in the migrating neural crest of Xenopus and zebrafish embryos. Loss-of-function studies using an antisense morpholino against syn4 show that this molecule is required for NC migration, but not for NC induction. Inhibition of Syn4 does not affect the velocity of cell migration, but significantly reduces the directional migration of NC cells. Furthermore, we show that Syn4 and PCP signaling control the directional migration of NC cells by regulating the direction in which the cell protrusions are generated during migration. Finally, we perform FRET analysis of Cdc42, Rac and RhoA in vitro and in vivo after interfering with Syn4 and PCP signaling. This is the first time that FRET analysis of small GTPases has been performed in vivo. Our results show that Syn4 inhibits Rac activity, whereas PCP signaling promotes RhoA activity. In addition, we show that RhoA inhibits Rac in NC cells. We present a model in which Syn4 and PCP control directional NC migration by, at least in part, regulating membrane protrusions through the regulation of small GTPase activities.

Related Papers

• → Activation of Small GTPases RhoA and Rac1 Is Required for Avian Reovirus p10-induced Syncytium Formation(2008)28 cited
• → RhoA and Rac1 signals in fMLP-induced NF-κB activation in human blood monocytes(2004)10 cited
• → RhoA and Rac1 signals in fMLP-induced NF-$kappa;B activation in human blood monocytes(2004)1 cited
• → Abstract 3847: Cytoplasmic ECT2: Implications for invasion and migration and RAS-RAC cross-talk in glioma(2011)
• → RhoA/ROCK-mediated switching between Cdc42- and Rac1-dependent protrusion in MTLn3 carcinoma cells(2020)