Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 288, Issue 30, Pages 22174-22183Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M113.463620
Keywords
Craniofacial Development; Fibroblast Growth Factor (FGF); Fibroblast Growth Factor Receptor (FGFR); Transgenic Mice; Tyrosinase
Categories
Funding
- National Institutes of Health [K08DE020883]
- USPHS [CA96824, CA140388]
- Natural Science Foundation of Zhejiang Province of China [Y2110492]
- J. S. Dunn Research Foundation
- Cancer Prevention and Research Institution of Texas [CPRIT110555]
- National Natural Science Foundation of China [81101712, 81270761]
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Cleft palate is a common congenital birth defect. The fibroblast growth factor (FGF) family has been shown to be important for palatogenesis, which elicits the regulatory functions by activating the FGF receptor tyrosine kinase. Mutations in Fgf or Fgfr are associated with cleft palate. To date, most mechanistic studies on FGF signaling in palate development have focused on FGFR2 in the epithelium. Although Fgfr1 is expressed in the cranial neural crest (CNC)-derived palate mesenchyme and Fgfr1 mutations are associated with palate defects, how FGFR1 in palate mesenchyme regulates palatogenesis is not well understood. Here, we reported that by using Wnt1(Cre) to delete Fgfr1 in neural crest cells led to cleft palate, cleft lip, and other severe craniofacial defects. Detailed analyses revealed that loss-of-function mutations in Fgfr1 did not abrogate patterning of CNC cells in palate shelves. However, it upset cell signaling in the frontofacial areas, delayed cell proliferation in both epithelial and mesenchymal compartments, prevented palate shelf elevation, and compromised palate shelf fusion. This is the first report revealing how FGF signaling in CNC cells regulates palatogenesis.
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