title: Mesenchymal fibroblast growth factor receptor signaling regulates palatal shelf elevation during secondary palate formation.
abstract: BACKGROUND
  Palatal shelf elevation is an essential morphogenetic process during secondary palate closure and failure or delay of palatal shelf elevation is a common cause of cleft palate, one of the most common birth defects in humans. Here, we studied the role of mesenchymal fibroblast growth factor receptor (FGFR) signaling during palate development by conditional inactivation of Fgfrs using a mesenchyme-specific Dermo1-Cre driver.
  
  
  RESULTS
  We showed that Fgfr1 is expressed throughout the palatal mesenchyme and Fgfr2 is expressed in the medial aspect of the posterior palatal mesenchyme overlapping with Fgfr1. Mesenchyme-specific disruption of Fgfr1 and Fgfr2 affected palatal shelf elevation and resulted in cleft palate. We further showed that both Fgfr1 and Fgfr2 are expressed in mesenchymal tissues of the mandibular process but display distinct expression patterns. Loss of mesenchymal FGFR signaling reduced mandibular ossification and lower jaw growth resulting in abnormal tongue insertion in the oral-nasal cavity.
  
  
  CONCLUSIONS
  We propose a model to explain how redundant Fgfr1 and Fgfr2 expression in the palatal and mandibular mesenchyme regulates shelf medial wall protrusion and growth of the mandible to coordinate the craniofacial tissue movements that are required for palatal shelf elevation.
authors.affiliation: Division of Craniofacial Medicine, Department of Pediatrics, University of Washington and Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, Seattle, Washington.
authors.forename: Kai
authors.initials: K
authors.lastname: Yu
authors.affiliation: Department of Developmental Biology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Kannan
authors.initials: K
authors.lastname: Karuppaiah
authors.affiliation: Department of Developmental Biology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: David M
authors.initials: DM
authors.lastname: Ornitz
mesh_terms: D000818:Animals; D002972:Cleft Palate / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D017403:In Situ Hybridization; D008334:Mandible / Q000196:embryology / Q000502:physiology; D008648:Mesoderm / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009024:Morphogenesis / Q000235:genetics; D010159:Palate / Q000196:embryology*; D010641:Phenotype; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics / Q000502:physiology*; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction
chemical_list: C496349:Fgfr1 protein, mouse; C496354:Fgfr2 protein, mouse; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2
keywords: FGFR gene expression; cleft palate; conditional gene knockout; mandible development; palatal shelf elevation; secondary palate development