The receptor tyrosine kinase Ror2 is a major Wnt receptor that activates β-catenin-independent signaling and plays a conserved role in the regulation of convergent extension movements and planar cell polarity in vertebrates. Mutations in the ROR2 gene cause recessive Robinow syndrome in humans, a short-limbed dwarfism associated with craniofacial malformations. Here, we show that Ror2 is required for local upregulation of gdf6 at the neural plate border in Xenopus embryos. Ror2 morphant embryos fail to upregulate neural plate border genes and show defects in the induction of neural crest cell fate. These embryos lack the spatially restricted activation of BMP signaling at the neural plate border at early neurula stages, which is required for neural crest induction. Ror2-dependent planar cell polarity signaling is required in the dorsolateral marginal zone during gastrulation indirectly to upregulate the BMP ligand Gdf6 at the neural plate border and Gdf6 is sufficient to rescue neural plate border specification in Ror2 morphant embryos. Thereby, Ror2 links Wnt/planar cell polarity signaling to BMP signaling in neural plate border specification and neural crest induction.
The authors declare no competing or financial interests.
C.S. carried out experiments, documented and interpreted results. M.B. and A.B. designed and carried out statistical analysis. A.S. conceived of the study, participated in its design, coordination and data analysis and wrote the manuscript.
This work was supported by the Deutsche Forschungsgemeinschaft in the frame of Research Unit 942 [grant numbers SCHA965/7-2 to A.S. and BE 2552/4-2 to A.B.].
Supplementary information available online at http://dev.biologists.org/lookup/doi/10.1242/dev.135426.supplemental
- Received January 17, 2016.
- Accepted July 25, 2016.