Cranial neural crest deletion of VEGFa causes cleft palate with aberrant vascular and bone development
Autor: | Scott Baldwin, Sarah L. Rohde, Britni Jacobs, Steven Goudy, Lucy Kennedy, Bin Zhou, Cynthia R. Hill |
---|---|
Rok vydání: | 2014 |
Předmět: |
Vascular Endothelial Growth Factor A
Histology Angiogenesis Mesenchyme Mice Transgenic Pathology and Forensic Medicine Mesoderm Cranial neural crest medicine Morphogenesis Animals Craniofacial Cell Proliferation Bone Development business.industry Ossification Skull Gene Expression Regulation Developmental Cell Biology Anatomy Cleft Palate Vascular endothelial growth factor A medicine.anatomical_structure Normal ossification Neural Crest Intramembranous ossification Blood Vessels medicine.symptom business Signal Transduction |
Zdroj: | Cell and tissue research. 361(3) |
ISSN: | 1432-0878 |
Popis: | 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. |
Databáze: | OpenAIRE |
Externí odkaz: |