Neural crest specification by noncanonical Wnt signaling and PAR-1

Abstract

SUMMARYNeural 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/b-catenin pathway in NC specification has been well established, a similar role for Wnt proteins that do not stabilize bcatenin 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 b-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.

Ror2 Receptor Mediates Wnt11 Ligand Signaling and Affects Convergence and Extension Movements in Zebrafish

“…In addition to Wnt11, the noncanonical Wnt ligands Wnt4a and Wnt11-related are also required and act non-redundantly to control specific aspects of convergence and extension. However, their associated receptors have not been identified (13,52).…”

Signaling pathways and tissue interactions in neural plate border formation

“…Expression of NPB markers in Ror2-depleted embryos was restored by a PCP-activating mutant of DVL, which lacks the DIX domain, 51 and by both Xenopus PCDH8 paralogs, PAPC and PCNS, which is consistent with a previous study on the role of PCP signaling in post-gastrula NC induction. 52 At early neurula stages, the elevation of the neural folds marks the onset of neurulation. At the same time, the gdf6-positive NPB has concomitantly thickened, suggesting that also the NBP undergoes morphogenetic changes.…”

Vangl2 cooperates with Rab11 and Myosin V to regulate apical constriction during vertebrate gastrulation

“…The RT-PCR primers were as follows: Gsc forward, 5′-GAACAGCTGGCAAGGAGAGT-3; and Gsc reverse, 5′-GATCTTT-TCTGCCTCCTCCA-3′; Odc forward, 5′-CATCTTTCACCCTGGCAG-TT-3′; and Odc reverse, 5′-CATTGGCAGCATCTTCTTCA-3′; Gef3.2 (GenBank accession number NM_001096674.1) forward, 5′-AGTGGG-TTTCAAAAATGGAT-3′; and Gef3.2 reverse, 5′-CTTTCAACCTCCTC-CTTGTT-3′. The primers for other genes, including Chordin (Hikasa and Sokol, 2004), FoxD3 (Ossipova et al, 2011) and Xbra (Agius et al, 2000), were as described previously.…”