Cell polarity of neural crest-derived mesenchymal cells controls craniofacial development

Abstract Cell polarity is essential for tissue organization during development. While the molecular mechanisms governing epithelial cell polarity are well understood, the polarity of mesenchymal cells remains under debate. Using a mouse model with Wnt5a deletion in cranial neural crest cells, we analyzed polarized intracellular components that regulate mesenchymal cell organization, proliferation, and migration prior to mesenchymal condensation in the craniofacial region. Loss of Wnt5a disrupted the polarized localization of primary cilia and the Golgi apparatus along the proximal-distal axis. This intracellular disorganization impaired the orientation of the cell division plane and was accompanied by a reduced proliferation rate. As a result, several distal facial structures, including the frontonasal cartilage, premaxilla, and distal mandible, were significantly reduced in Wnt5a conditional mutants.