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Elife July 23, 2018; 7
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Dkk2 promotes neural crest specification by activating Wnt/β-catenin signaling in a GSK3β independent manner.

Devotta A , Hong CS , Saint-Jeannet JP .

Neural crest progenitors are specified through the modulation of several signaling pathways, among which the activation of Wnt/β-catenin signaling by Wnt8 is especially critical. Glycoproteins of the Dickkopf (Dkk) family are important modulators of Wnt signaling acting primarily as Wnt antagonists. Here we report that Dkk2 is required for neural crest specification functioning as a positive regulator of Wnt/β-catenin signaling. Dkk2 depletion in Xenopus embryos causes a loss of neural crest progenitors, a phenotype that is rescued by expression of Lrp6 or β-catenin. Dkk2 overexpression expands the neural crest territory in a pattern reminiscent of Wnt8, Lrp6 and β-catenin gain-of-function phenotypes. Mechanistically, we show that Dkk2 mediates its neural crest-inducing activity through Lrp6 and β-catenin, however unlike Wnt8, in a GSK3β independent manner. These findings suggest that Wnt8 and Dkk2 converge on β-catenin using distinct transduction pathways both independently required to activate Wnt/β-catenin signaling and induce neural crest cells.

PubMed ID: 30035713
PMC ID: PMC6056231
Article link: Elife
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: actc1 ctnnb1 dct dkk1 dkk2 eef1a2 fgf8 gsk3b krt12.4 krt70 lrp5 lrp6 myod1 nog pax3 pcdh8 pcdh8.2 snai1 snai2 sox10 sox2 sox8 sox9 tbxt twist1 wnt8a
GO keywords: neural crest cell fate specification [+]
Morpholinos: ctnnb1 MO1 dkk2 MO1 dkk2 MO2 lrp6 MO1 wnt8a MO1

Article Images: [+] show captions
References [+] :
Aoki, Sox10 regulates the development of neural crest-derived melanocytes in Xenopus. 2003, Pubmed, Xenbase