Wnt5a regulates directional cell migration and cell proliferation via Ror2‐mediated noncanonical pathway in mammalian palatogenesis

Abstract

Tissue and molecular heterogeneities are present in the developing secondary palate along the anterior‐posterior (A‐P) axis in mice. Here we show that Wnt5a and its receptor Ror2 are expressed in a graded manner along the A‐P axis of the palate. Wnt5a‐deficiency leads to a complete cleft of the secondary palate, which exhibits distinct phenotypic alterations at histology, cellular, and molecular levels in the anterior and posterior regions of the palate. We demonstrate that there is directional cell migration within the developing palate. In the absence of Wnt5a, this directional cell migration does not occur. Genetic studies and in vitro organ culture assays further demonstrate a role for Ror2 in mediating Wnt5a signaling in the regulation of cell proliferation and migration during palate development. Our results reveal distinct regulatory roles for Wnt5a in gene expression and cell proliferation along the A‐P axis of the developing palate and an essential role of Wnt5a in the regulation of directional cell migration.