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Cranial neural crest deletion of VEGFa causes cleft palate with aberrant vascular and bone development

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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.

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Authors and Affiliations

  1. Department of Otolaryngology, Vanderbilt School of Medicine, 7309 21st Ave South, Nashville, TN, 27232, USA

    Cynthia Hill, Britni Jacobs, Lucy Kennedy, Sarah Rohde & Steven Goudy

  2. Department of Genetics, Albert Einstein College of Medicine, 1301 Morris Park Ave, Bronx, NY, 20461, USA

    Bin Zhou

  3. Department of Pediatrics, Vanderbilt School of Medicine, 2200 Children’s Way, Nashville, TN, 37232, USA

    Scott Baldwin

Authors
  1. Cynthia Hill
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  2. Britni Jacobs
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  3. Lucy Kennedy
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  4. Sarah Rohde
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  5. Bin Zhou
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  6. Scott Baldwin
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  7. Steven Goudy
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Correspondence to Cynthia Hill.

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Hill, C., Jacobs, B., Kennedy, L. et al. Cranial neural crest deletion of VEGFa causes cleft palate with aberrant vascular and bone development. Cell Tissue Res 361, 711–722 (2015). https://doi.org/10.1007/s00441-015-2150-7

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  • DOI: https://doi.org/10.1007/s00441-015-2150-7

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