Neural crest cell-derived VEGF promotes embryonic jaw extension
Date
2015
Authors
Wiszniak, S.
Mackenzie, F.E.
Anderson, P.
Kabbara, S.
Ruhrberg, C.
Schwarz, Q.
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Journal article
Citation
Proceedings of the National Academy of Sciences of the United States of America, 2015; 112(19):6086-6091
Statement of Responsibility
Sophie Wiszniak, Francesca E. Mackenzie, Peter Anderson, Samuela Kabbara, Christiana Ruhrberg, and Quenten Schwarz
Conference Name
Abstract
Jaw morphogenesis depends on the growth of Meckel's cartilage during embryogenesis. However, the cell types and signals that promote chondrocyte proliferation for Meckel's cartilage growth are poorly defined. Here we show that neural crest cells (NCCs) and their derivatives provide an essential source of the vascular endothelial growth factor (VEGF) to enhance jaw vascularization and stabilize the major mandibular artery. We further show in two independent mouse models that blood vessels promote Meckel's cartilage extension. Coculture experiments of arterial tissue with NCCs or chondrocytes demonstrated that NCC-derived VEGF promotes blood vessel growth and that blood vessels secrete factors to instruct chondrocyte proliferation. Computed tomography and X-ray scans of patients with hemifacial microsomia also showed that jaw hypoplasia correlates with mandibular artery dysgenesis. We conclude that cranial NCCs and their derivatives provide an essential source of VEGF to support blood vessel growth in the developing jaw, which in turn is essential for normal chondrocyte proliferation, and therefore jaw extension.
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Freely available online through the PNAS open access option.