title: Cranial neural crest deletion of VEGFa causes cleft palate with aberrant vascular and bone development.
abstract: Cleft palate is among the most common craniofacial congenital anomalies. Up to 30% of patients with cleft palate also have associated cardiac and vascular defects. VEGFa, a critical growth factor involved in multiple developmental processes including angiogenesis and ossification, is also required for palate development. Conditional deletion of VEGFa in cranial neural crest (CNC) cells using Wnt1-Cre (VEGFaCKO) resulted in cleft palate in mice. The phenotype included reduced proliferation of cells within the palatal shelves, abnormal palatal shelf elongation and elevation, and the inability to undergo fusion. Vascularization of the VEGFaCKO palatal shelves was greatly reduced, suggesting a non-cell autonomous role of VEGFa signaling from the CNC-derived cells to the endothelium during vessel formation. Defective vascular development was coupled with deficient intramembranous ossification of maxillary and palatal mesenchyme. In vitro assessment of CNC-derived palatal mesenchymal cells from VEGFaCKO mice demonstrated normal ossification after BMP2 stimulation, suggesting that inadequate expression of Bmp2 in VEGFaCKO mice was, in part, responsible for reduced ossification. Taken together, these data demonstrate that VEGFa produced in the CNC-derived mesenchyme drives proliferation, vascularization, and ossification, all of which are critical for palate development.
authors.affiliation: Department of Otolaryngology, Vanderbilt School of Medicine, 7309 21st Ave South, Nashville, TN, 27232, USA, cynthia.r.allison@vanderbilt.edu.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Hill
authors.forename: Britni
authors.initials: B
authors.lastname: Jacobs
authors.forename: Lucy
authors.initials: L
authors.lastname: Kennedy
authors.forename: Sarah
authors.initials: S
authors.lastname: Rohde
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
authors.forename: Scott
authors.initials: S
authors.lastname: Baldwin
authors.forename: Steven
authors.initials: S
authors.lastname: Goudy
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000196:embryology / Q000378:metabolism; D001846:Bone Development / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D008648:Mesoderm; D008822:Mice, Transgenic; D009024:Morphogenesis / Q000235:genetics; D009432:Neural Crest / Q000166:cytology*; D015398:Signal Transduction / Q000502:physiology; D012886:Skull / Q000196:embryology / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse