Neural crest cell-derived VEGF promotes embryonic jaw extension.
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.
Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, SA 5000, Australia;
Sophie
S
Wiszniak
UCL Institute of Ophthalmology, University College London, London EC1V 9EL, United Kingdom;
Francesca E
FE
Mackenzie
Australian Craniofacial Unit, Adelaide, SA 5000, Australia; and Faculty of Health Sciences, University of Adelaide, Adelaide, SA 5000, Australia.
Peter
P
Anderson
Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, SA 5000, Australia;
Samuela
S
Kabbara
UCL Institute of Ophthalmology, University College London, London EC1V 9EL, United Kingdom; quenten.schwarz@health.sa.gov.au c.ruhrberg@ucl.ac.uk.
Christiana
C
Ruhrberg
Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, SA 5000, Australia; quenten.schwarz@health.sa.gov.au c.ruhrberg@ucl.ac.uk.
Quenten
Q
Schwarz
D000293:Adolescent; D000818:Animals; D002356:Cartilage / Q000196:embryology; D002454:Cell Differentiation; D049109:Cell Proliferation; D019902:Chondrocytes / Q000378:metabolism; D018920:Coculture Techniques; D005260:Female; D006053:Goldenhar Syndrome / Q000000981:diagnostic imaging / Q000503:physiopathology*; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008334:Mandible / Q000002:abnormalities* / Q000098:blood supply / Q000196:embryology*; D051379:Mice; D009432:Neural Crest / Q000166:cytology / Q000378:metabolism*; D014057:Tomography, X-Ray Computed; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D051155:Wnt1 Protein / Q000235:genetics
C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse; C467480:vascular endothelial growth factor A, mouse
VEGF; blood vessel; chondrocyte; mandible; neural crest