Directed cell migration is crucially important for development, and is a feature of neural crest (NC) cells, which have remarkable migratory abilities. On , Roberto Mayor and colleagues investigate how NC cells keep to the right path in zebrafish and Xenopus embryos, by studying the effects of a proteoglycan, Syndecan-4 (Syn4), on NC migration. Syn4, they report, is essential for directional NC migration, and directs NC cell movement by regulating the polarised formation of membrane protrusions, in a manner similar to that of non-canonical Wnt/planar cell polarity (PCP) signalling. To investigate how Syn4 orientates cell protrusions, the authors used in vivo FRET analysis to measure the localised activity of several small GTPases involved in cell migration. Syn4, they discovered, inhibits Rac activity, a small GTPase that controls cytoskeletal dynamics and cell adhesion, while PCP signalling activates RhoA, which also inhibits Rac in NC cells. Thus Syn4 and PCP signalling seemingly control directional NC migration by regulating membrane protrusions by inhibiting Rac at the back of the cell.
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