Journal Article

Neural crest cell-derived VEGF promotes embryonic jaw extension

Wiszniak, Sophie, Kabbara, Samuela, Ruhrberg, Christiana, Schwarz, Quenten, Anderson, Peter, Mackenzie, Francesca E.

2015

Overview

Significance Craniofacial development is a complex morphogenic event that relies on highly orchestrated interactions between multiple cell types. Since the first description of Meckel’s cartilage in the lower jaw more than 180 years ago, we have come to realize that expansion of this specialized structure underpins correct mandible development. Here we demonstrate that an intricate association between neural crest cells and blood vessels plays an important role in promoting chondrocyte proliferation and expansion of Meckel’s cartilage as a prerequisite of correct mandibular morphogenesis. These findings provide direct insight into the origins and potential treatments of highly prevalent disorders affecting the mandible. 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.

• Publisher: National Academy of Sciences
• Subject: Adolescent / Animals / Biological Sciences / Blood vessels / Cartilage / Cartilage - embryology / Cell Differentiation / Cell Proliferation / Cells / Chondrocytes - metabolism / Coculture Techniques / Computed tomography / Developmental Biology / Embryonic growth stage / Experiments / Female / Goldenhar Syndrome - diagnostic imaging / Goldenhar Syndrome - physiopathology / Humans / In Situ Hybridization / Male / Mandible - abnormalities / Mandible - blood supply / Mandible - embryology / Mice / morphogenesis / neural crest / Neural Crest - cytology / Neural Crest - metabolism / Prenatal development / Rodents / Tomography, X-Ray Computed / Vascular endothelial growth factor / Vascular Endothelial Growth Factor A - metabolism / vascular endothelial growth factors / Wnt1 Protein - genetics