title: Type 1 fibroblast growth factor receptor in cranial neural crest cell-derived mesenchyme is required for palatogenesis.
abstract: 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.
authors.affiliation: College of Pharmacy, Wenzhou Medical College, Wenzhou, Zhejiang 325000, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Wang
authors.forename: Julia Yu Fong
authors.initials: JY
authors.lastname: Chang
authors.forename: Chaofeng
authors.initials: C
authors.lastname: Yang
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Huang
authors.forename: Junchen
authors.initials: J
authors.lastname: Liu
authors.forename: Pan
authors.initials: P
authors.lastname: You
authors.forename: Wallace L
authors.initials: WL
authors.lastname: McKeehan
authors.forename: Fen
authors.initials: F
authors.lastname: Wang
authors.forename: Xiaokun
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002972:Cleft Palate / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000196:embryology / Q000378:metabolism; D004848:Epithelium / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D007763:Lac Operon / Q000235:genetics; D008648:Mesoderm / Q000196:embryology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009432:Neural Crest / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D010159:Palate / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D022661:RNA, Untranslated; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D013997:Time Factors; D046509:Tissue Culture Techniques
chemical_list: C110853:Gt(ROSA)26Sor non-coding RNA, mouse; D011506:Proteins; D022661:RNA, Untranslated; C496349:Fgfr1 protein, mouse; D051496:Receptor, Fibroblast Growth Factor, Type 1
keywords: Craniofacial Development; Fibroblast Growth Factor (FGF); Fibroblast Growth Factor Receptor (FGFR); Transgenic Mice; Tyrosinase