Minghui Yue1, Yu Lan1,2,3,4,5, Han Liu1, Zhaoming Wu1, Toru Imamura6, Rulang Jiang1,2,3,4,5. 1. Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA. 2. Division of Plastic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA. 3. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA. 4. Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA. 5. Shriners Hospitals for Children, Cincinnati, Ohio, USA. 6. Cell Regulation Laboratory, School of Bioscience and Biotechnology, Tokyo University of Technology, Tokyo, Japan.
Abstract
BACKGROUND: Previous studies showed that mice lacking Fgf18 function had cleft palate defects and that the FGF18 locus was associated with cleft lip and palate in humans, but what specific roles Fgf18 plays during palatogenesis are unclear. RESULTS: We show that Fgf18 exhibits regionally restricted expression in developing palatal shelves, mandible, and tongue, during palatal outgrowth and fusion in mouse embryos. Tissue-specific inactivation of Fgf18 throughout neural crest-derived craniofacial mesenchyme caused shortened mandible and reduction in ossification of the frontal, nasal, and anterior cranial base skeletal elements in Fgf18c/c ;Wnt1-Cre mutant mice. About 64% of Fgf18c/c ;Wnt1-Cre mice exhibited cleft palate. Whereas palatal shelf elevation was impaired in many Fgf18c/c ;Wnt1-Cre embryos, no significant difference in palatal cell proliferation was detected between Fgf18c/c ;Wnt1-Cre embryos and their control littermates. Embryonic maxillary explants from Fgf18c/c ;Wnt1-Cre embryos showed successful palatal shelf elevation and fusion in organ culture similar to the maxillary explants from control embryos. Furthermore, tissue-specific inactivation of Fgf18 in the early palatal mesenchyme did not cause cleft palate. CONCLUSION: These results demonstrate a critical role for Fgf18 expression in the neural crest-derived mesenchyme for the development of the mandible and multiple craniofacial bones but Fgf18 expression in the palatal mesenchyme is dispensable for palatogenesis.
BACKGROUND: Previous studies showed that mice lacking Fgf18 function had cleft palate defects and that the FGF18 locus was associated with cleft lip and palate in humans, but what specific roles Fgf18 plays during palatogenesis are unclear. RESULTS: We show that Fgf18 exhibits regionally restricted expression in developing palatal shelves, mandible, and tongue, during palatal outgrowth and fusion in mouse embryos. Tissue-specific inactivation of Fgf18 throughout neural crest-derived craniofacial mesenchyme caused shortened mandible and reduction in ossification of the frontal, nasal, and anterior cranial base skeletal elements in Fgf18c/c ;Wnt1-Cre mutant mice. About 64% of Fgf18c/c ;Wnt1-Cre mice exhibited cleft palate. Whereas palatal shelf elevation was impaired in many Fgf18c/c ;Wnt1-Cre embryos, no significant difference in palatal cell proliferation was detected between Fgf18c/c ;Wnt1-Cre embryos and their control littermates. Embryonic maxillary explants from Fgf18c/c ;Wnt1-Cre embryos showed successful palatal shelf elevation and fusion in organ culture similar to the maxillary explants from control embryos. Furthermore, tissue-specific inactivation of Fgf18 in the early palatal mesenchyme did not cause cleft palate. CONCLUSION: These results demonstrate a critical role for Fgf18 expression in the neural crest-derived mesenchyme for the development of the mandible and multiple craniofacial bones but Fgf18 expression in the palatal mesenchyme is dispensable for palatogenesis.
Authors: Jun Han; Julie Mayo; Xun Xu; Jingyuan Li; Pablo Bringas; Richard L Maas; John L R Rubenstein; Yang Chai Journal: Development Date: 2009-12 Impact factor: 6.868
Authors: Ritva Rice; Bradley Spencer-Dene; Elaine C Connor; Amel Gritli-Linde; Andrew P McMahon; Clive Dickson; Irma Thesleff; David P C Rice Journal: J Clin Invest Date: 2004-06 Impact factor: 14.808