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Development 2011 Dec 01;13824:5441-50. doi: 10.1242/dev.067280.
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Neural crest specification by noncanonical Wnt signaling and PAR-1.

Ossipova O , Sokol SY .

Neural crest (NC) cells are multipotent progenitors that form at the neural plate border, undergo epithelial-mesenchymal transition and migrate to diverse locations in vertebrate embryos to give rise to many cell types. Multiple signaling factors, including Wnt proteins, operate during early embryonic development to induce the NC cell fate. Whereas the requirement for the Wnt/β-catenin pathway in NC specification has been well established, a similar role for Wnt proteins that do not stabilize β-catenin has remained unclear. Our gain- and loss-of-function experiments implicate Wnt11-like proteins in NC specification in Xenopus embryos. In support of this conclusion, modulation of β-catenin-independent signaling through Dishevelled and Ror2 causes predictable changes in premigratory NC. Morpholino-mediated depletion experiments suggest that Wnt11R, a Wnt protein that is expressed in neuroectoderm adjacent to the NC territory, is required for NC formation. Wnt11-like signals might specify NC by altering the localization and activity of the serine/threonine polarity kinase PAR-1 (also known as microtubule-associated regulatory kinase or MARK), which itself plays an essential role in NC formation. Consistent with this model, PAR-1 RNA rescues NC markers in embryos in which noncanonical Wnt signaling has been blocked. These experiments identify novel roles for Wnt11R and PAR-1 in NC specification and reveal an unexpected connection between morphogenesis and cell fate.

PubMed ID: 22110058
PMC ID: PMC3222216
Article link: Development
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: ctnnb1 dvl2 foxd3 hes4 krt70 mark2 mark3 myc myod1 ocln pax3 ror2 snai2 sox2 sox3 sox8 tfap2a twist1 wnt11
Morpholinos: mark2 MO1 mark2 MO2 ror2 MO1 wnt11 MO1 wnt11 MO2

Article Images: [+] show captions
References [+] :
Acloque, Epithelial-mesenchymal transitions: the importance of changing cell state in development and disease. 2009, Pubmed