Wnt2bb signaling promotes pharyngeal chondrogenic precursor proliferation and chondrocyte maturation by activating Yap expression in zebrafish.

Pharyngeal cartilage morphogenesis is crucial for the formation of craniofacial structures. Cranial neural crest cells are specified at the neural plate border, migrate to pharyngeal arches, and differentiate into pharyngeal chondrocytes, which subsequently flatten, elongate, and stack like coins during maturation. Although the developmental processes prior to chondrocyte maturation have been extensively studied, their subsequent changes in morphology and organization remain largely elusive. Here, we show that wnt2bb is expressed in the pharyngeal ectoderm adjacent to the chondrogenic precursor cells in zebrafish. Inactivation of Wnt2bb leads to a reduction in nuclear β-catenin, which impairs chondrogenic precursor proliferation and disrupts chondrocyte morphogenesis and organization, eventually causing a severe shrinkage of pharyngeal cartilages. Moreover, the decrease of β-catenin in wnt2bb^-/- mutants is accompanied by the reduction of Yap expression. Reactivation of Yap can restore the proliferation of chondrocyte progenitors as well as the proper size, shape, and stacking of pharyngeal chondrocytes. Our findings suggest that Wnt/β-catenin signaling promotes Yap expression to regulate pharyngeal cartilage formation in zebrafish.