Editors' ChoiceDevelopment

WNTs Hitch a Ride

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Sci. Signal.  13 May 2014:
Vol. 7, Issue 325, pp. ec126
DOI: 10.1126/scisignal.2005466

During embryonic development, cells of the neural epithelium signal to somites to coordinate differentiation and patterning. WNT1 and WNT3A produced by the dorsal neural tube activate β-catenin signaling in the dermomyotome, a dorsal region of somites that differentiates into muscle cells. β-catenin activates expression of WNT11, and WNT11 activates β-catenin–independent signaling to polarize developing myotubes along the anterior posterior axis. Trunk neural crest cells undergo an epithelial to mesenchymal transition to leave the dorsal neural tube and migrate ventrally adjacent to developing somites. Serralbo et al. found that neural crest cells carry WNTs from the dorsal neural tube to the dermomyotome. In both mouse and chick embryos, WNT1 localized on migratory cells that were positive for neural crest cell markers. Electroporation of the chick dorsal neural tube with plasmids that encoded factors that either killed neural crest cells or prevented their migration reduced the expression of WNT11 mRNA in the dermomyotome and disrupted polarization of myotubes. glypican-4 is a cell surface heparan sulfate proteoglycan that is related to other glypicans that affect WNT distribution and promote WNT signaling, and the mRNA encoding glypican-4 was expressed in migratory neural crest cells. Knockdown of glypican-4 in the dorsal neural tube by electroporation of short interfering RNAs reduced activation of a β-catenin reporter in migrating neural crest cells, inhibited the expression of WNT11 mRNA in the dermomyotome, and disrupted the polarization of myotubes. Knockdown of glypican-4 in somites did not affect WNT11 expression, suggesting that glypican-4 acts in cis with WNT1 on neural crest cells to activate autocrine β-catenin signaling and may also present WNT1 to cells in the dorsal dermomyotome. Thus, migratory neural crest cells convey critical long-range signals that coordinate development of the ectoderm and mesoderm.

O. Serralbo, C. Marcelle, Migrating cells mediate long-range Wnt signaling. Development 141, 2057–2063 (2014). [Abstract] [Full Text]