The BMP ligand Gdf6a Regulates Development of the Zebrafish Craniofacial Skeleton in a Pharyngeal Arch-Specific Manner

Abstract

Craniofacial development involves the concerted action of several different tissue types and cellular processes that must be intricately regulated. Here, we describe the role of the BMP ligand Growth and Differentiation Factor 6a (gdf6a) in the development of the zebrafish craniofacial skeleton. Larval gdf6a mutant zebrafish have malformations in the midline of the craniofacial skeleton that correlate with the expression of gdf6a in the embryonic pharyngeal arches. We show that Gdf6a has arch-specific roles in craniofacial morphogenesis; Gdf6a promotes chondrogenesis and alignment of midline craniofacial elements in the posterior pharyngeal arches (arches 2 and 3) and regulates morphogenesis within the mandibular symphysis of pharyngeal arch 1. We demonstrate that Gdf6a regulates craniofacial development through activation of canonical BMP signaling, likely acting cooperatively with additional BMP ligands. Taken together, this work elucidates how Gdf6a/BMP signaling directs development of the craniofacial skeleton, specifically along the ventral midline. Summary StatementGdf6a regulates the development of the midline structures in the zebrafish craniofacial skeleton in an arch-specific manner via canonical BMP signaling.