IGF1 from blood vessels promotes growth of the jaw

Meckel's cartilage is a transient structure in the lower jaw that acts as a template for subsequent bone deposition. Appropriate proliferation of chondrocytes within this cartilage is therefore essential to define proper jaw length. Sophie Wiszniak, Quenten Schwarz and colleagues have previously shown that angiocrine factors – released from the mandibular vessels surrounding the developing cartilage – promote chondrocyte proliferation. Now, they identify the IGF1 ligand as a key vessel-derived factor for Meckel's cartilage growth. They first show that IGF1 is present in aorta-conditioned media, and can promote proliferation of chondrocytes in culture. In mice, complete Igf1 knockouts are known to have strong skeletal phenotypes, but chondrocyte-specific Igf1 depletion has only a mild effect. The authors show that endothelial-specific knockout of Igf1 leads to reduced Meckel's cartilage length and smaller overall head size. Finally, IGF1 can rescue the growth defect of Meckel's cartilage explants derived from mice in which the mandibular vessels are absent. Thus, this work reveals vessel-derived IGF1 as an important regulator of facial skeletal development, adding to a growing body of work showing how angiocrine signals can influence the development of a wide range of tissues.