VEGF stimulates intramembranous bone formation during craniofacial skeletal development

•VEGF produced by Osx + osteoblast progenitor cells is required for optimal intramembranous ossification.•VEGF derived from Osx + precursors suppresses proliferation of cells in the jaw mesenchyme.•The mechanisms by which VEGF controls mandibular osteogenesis likely involve BMP-dependent specification of jaw mesenchyme.

Deficiency of vascular endothelial growth factor A (VEGF) has been associated with severe craniofacial anomalies in both humans and mice. Cranial neural crest cell (NCC)-derived VEGF regulates proliferation, vascularization and ossification of cartilage and membranous bone. However, the function of VEGF derived from specific subpopulations of NCCs in controlling unique aspects of craniofacial morphogenesis is not clear. In this study a conditional knockdown strategy was used to genetically delete Vegfa expression in Osterix (Osx) and collagen II (Col2)-expressing NCC descendants. No major defects in calvaria and mandibular morphogenesis were observed upon knockdown of VEGF in the Col2+ cell population. In contrast, loss of VEGF in Osx+ osteoblast progenitor cells led to reduced ossification of calvarial and mandibular bones without affecting the formation of