Journal
DEVELOPMENT
Volume 135, Issue 10, Pages 1771-1780Publisher
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/dev.017350
Keywords
cell migration; neural crest; directionality; persistence; Syndecan-4; non-canonical wnt signaling; PCP; RhoA; Rac1
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Funding
- MRC [G117/506] Funding Source: UKRI
- Medical Research Council [G117/506] Funding Source: researchfish
- Biotechnology and Biological Sciences Research Council Funding Source: Medline
- Medical Research Council [G117/506] Funding Source: Medline
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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.
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