Signaling Pathways in Craniofacial Development: Insights from Rare Skeletal Disorders

In the developing embryo, signaling pathways define how the mesenchymal precursors of bone form individual skeletal elements with the proper size, shape, orientation, and integration. Disruptions to these signaling processes lead to a large variety of congenital conditions categorized as skeletal dysplasias. While individually these skeletal disorders are rare, collectively they represent a significant cause of disability in the United States. Here, we discuss how the study of these rare events in human development reveal novel and unexpected insights into signaling mechanisms that regulate normal skeletal development and, in the process, advance novel molecular-based therapies for treatment of rare and common bone diseases alike.