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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2003-12-5
pubmed:abstractText
In the developing mammalian tooth, the cranial neural crest derived dental mesenchyme consists of the dental papilla and dental follicle. The dental papilla gives rise to odontoblasts and dental pulp and the dental follicle gives rise to the periodontium, including the osteoblasts that contribute to the alveolar process. The alveolar process is a specialized intramembranous bone that forms the primary support structure for the dentition. The Msx1 gene controls many aspects of craniofacial development, as evidenced by craniofacial abnormalities seen in Msx1(-/-) mice, including the arrest of tooth development and the absence of the alveolar bone. Previous studies demonstrated that ectopic expression of Bmp4, a downstream target of Msx1, in the Msx1(-/-) dental mesenchyme rescued alveolar bone formation. Here we confirm an early requirement of BMP activity for alveolar bone formation. We show that the expression of Cbfa1 and Dlx5, two genes encode transcription factors that are critical for bone differentiation, overlaps with that of Msx1 and Bmp4 in the developing tooth and alveolar process. We have demonstrated that Dlx5 and Cbfa1 expression is down-regulated in Msx1(-/-) dental mesenchyme and that Msx1 and Bmp4 expression are unaltered in Cbfa1(-/-) mice. These data place Dlx5 and Cbfa1 downstream from the Msx1/Bmp4 in the genetic pathway that regulates tooth development. Ectopic expression of Bmp4 in Msx1 mutants restores the expression of Dlx5, but not Cbfa1, in the dental mesenchyme, and rescues the expression of both Dlx5 and Cbfa1 in the developing alveolar bone. Therefore, the early expression of Cfba1 in the dental mesenchyme appears dispensable for the development of the alveolar bone. Taken together with in vitro gene induction studies, our results demonstrate that BMP4 controls Dlx5 expression in dental mesenchyme, and functions upstream to both Dlx5 and Cbfa1 to regulate alveolar bone formation during tooth development.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0925-4773
pubmed:author
pubmed:issnType
Print
pubmed:volume
120
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1469-79
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:14654219-Alveolar Process, pubmed-meshheading:14654219-Animals, pubmed-meshheading:14654219-Bone Morphogenetic Protein 4, pubmed-meshheading:14654219-Bone Morphogenetic Proteins, pubmed-meshheading:14654219-Core Binding Factor Alpha 1 Subunit, pubmed-meshheading:14654219-Down-Regulation, pubmed-meshheading:14654219-Epistasis, Genetic, pubmed-meshheading:14654219-Gene Deletion, pubmed-meshheading:14654219-Gene Expression Regulation, Developmental, pubmed-meshheading:14654219-Genetic Complementation Test, pubmed-meshheading:14654219-Homeodomain Proteins, pubmed-meshheading:14654219-MSX1 Transcription Factor, pubmed-meshheading:14654219-Mesoderm, pubmed-meshheading:14654219-Mice, pubmed-meshheading:14654219-Mice, Knockout, pubmed-meshheading:14654219-Neoplasm Proteins, pubmed-meshheading:14654219-RNA, Messenger, pubmed-meshheading:14654219-Transcription Factors, pubmed-meshheading:14654219-Transcriptional Activation
pubmed:year
2003
pubmed:articleTitle
Msx1/Bmp4 genetic pathway regulates mammalian alveolar bone formation via induction of Dlx5 and Cbfa1.
pubmed:affiliation
Department of Cell and Molecular Biology, Tulane University, 2000 Stern Hall, 6400 Freret St, New Orleans, LA 70118, USA. zzhang 1@tulane.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.