Background: Phosphorylation of Dishevelled (Dvl) by casein kinase 1ϵ (CK1ϵ) is a key event in Wnt signal transduction.Results: Dvl3 residues phosphorylated by CK1ϵ were identified by proteomics and analyzed functionally.Conclusion: Individual phosphorylation events control different aspects of Dvl biology.Significance: CK1ϵ and Fzd5, a Wnt receptor, act on Dvl via distinct mechanism, suggesting that CK1ϵ is not directly downstream of Frizzled5.

BackgroundBone morphogenetic proteins regulate multiple processes in embryonic development, including early dorso-ventral patterning and neural crest development. BMPs activate heteromeric receptor complexes consisting of type I and type II receptor-serine/threonine kinases. BMP receptors Ia and Ib, also known as ALK3 and ALK6 respectively, are the most common type I receptors that likely mediate most BMP signaling events. Since early expression patterns and functions in Xenopus laevis development have not been described, we have addressed these questions in the present study.ResultsHere we have analyzed the temporal and spatial expression patterns of ALK3 and ALK6; we have also carried out loss-of-function studies to define the function of these receptors in early Xenopus development. We detected both redundant and non-redundant roles of ALK3 and ALK6 in dorso-ventral patterning. From late gastrula stages onwards, their expression patterns diverged, which correlated with a specific, non-redundant requirement of ALK6 in post-gastrula neural crest cells. ALK6 was essential for induction of neural crest cell fate and further development of the neural crest and its derivatives.ConclusionsALK3 and ALK6 both contribute to the gene regulatory network that regulates dorso-ventral patterning; they play partially overlapping and partially non-redundant roles in this process. ALK3 and ALK6 are independently required for the spatially restricted activation of BMP signaling and msx2 upregulation at the neural plate border, whereas in post-gastrula development ALK6 exerts a highly specific, conserved function in neural crest development.Electronic supplementary materialThe online version of this article (doi:10.1186/s12861-016-0101-5) contains supplementary material, which is available to authorized users.

CamKII is a novel binding partner of Arrb2/Dvl2 protein complexes and is required for convergent extension movements in Xenopus. CamKII physically and functionally interacts with Dvl2, whereas CamKII activity is antagonistically modulated by Dvl1 and Dvl3.

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 neural crest is a transient cell population that gives rise to various cell types of multiple tissues and organs in the vertebrate embryo. Neural crest cells arise from the neural plate border, a region localized at the lateral borders of the prospective neural plate. Temporally and spatially coordinated interaction with the adjacent tissues, the non-neural ectoderm, the neural plate and the prospective dorsolateral mesoderm, is required for neural plate border specification. Signaling molecules, namely BMP, Wnt and FGF ligands and corresponding antagonists are derived from these tissues and interact to induce the expression of neural plate border specific genes. The present mini-review focuses on the current understanding of how the NPB territory is formed and accentuates the need for coordinated interaction of BMP and Wnt signaling pathways and precise tissue communication that are required for the definition of the prospective NC in the competent ectoderm.