title: Augmented BMPRIA-mediated BMP signaling in cranial neural crest lineage leads to cleft palate formation and delayed tooth differentiation.
abstract: The importance of BMP receptor Ia (BMPRIa) mediated signaling in the development of craniofacial organs, including the tooth and palate, has been well illuminated in several mouse models of loss of function, and by its mutations associated with juvenile polyposis syndrome and facial defects in humans. In this study, we took a gain-of-function approach to further address the role of BMPR-IA-mediated signaling in the mesenchymal compartment during tooth and palate development. We generated transgenic mice expressing a constitutively active form of BmprIa (caBmprIa) in cranial neural crest (CNC) cells that contributes to the dental and palatal mesenchyme. Mice bearing enhanced BMPRIa-mediated signaling in CNC cells exhibit complete cleft palate and delayed odontogenic differentiation. We showed that the cleft palate defect in the transgenic animals is attributed to an altered cell proliferation rate in the anterior palatal mesenchyme and to the delayed palatal elevation in the posterior portion associated with ectopic cartilage formation. Despite enhanced activity of BMP signaling in the dental mesenchyme, tooth development and patterning in transgenic mice appeared normal except delayed odontogenic differentiation. These data support the hypothesis that a finely tuned level of BMPRIa-mediated signaling is essential for normal palate and tooth development.
authors.affiliation: Department of Cell and Molecular Biology, Tulane University, New Orleans, Louisiana, United States of America.
authors.forename: Lu
authors.initials: L
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Minkui
authors.initials: M
authors.lastname: Lin
authors.forename: Guohua
authors.initials: G
authors.lastname: Yuan
authors.forename: Guobin
authors.initials: G
authors.lastname: Yang
authors.forename: Yuqian
authors.initials: Y
authors.lastname: Zheng
authors.forename: Yiping
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000818:Animals; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000235:genetics / Q000378:metabolism*; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D001973:Bromodeoxyuridine; D002454:Cell Differentiation / Q000502:physiology; D002972:Cleft Palate / Q000209:etiology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008648:Mesoderm / Q000196:embryology*; D051379:Mice; D008822:Mice, Transgenic; D009432:Neural Crest / Q000196:embryology* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014070:Tooth / Q000196:embryology*
chemical_list: D019485:Bone Morphogenetic Proteins; C498212:Bmpr1a protein, mouse; D052005:Bone Morphogenetic Protein Receptors, Type I; D001973:Bromodeoxyuridine