Linked Life Data

19699732

Source:http://linkedlifedata.com/resource/pubmed/id/19699732

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2009-9-28
pubmed:abstractText
Transforming growth factor beta (TGFbeta) is known to play important roles in multiple developmental processes. One of the main functions is in skeletal development. Our previous studies demonstrated that loss of Tgfbr2 in Prx1Cre-expressing limb mesenchyme results in defects in the long bones and joints of mice. Here we show that loss of Tgfbr2 also results in defects in the development of the skull vault indicating Tgfbr2 has a critical role in intramembranous bone formation as well as endochondral bone formation. Mutant mice did not survive after birth and demonstrated an open skull. The first signs of skull defects were observed at E14.5 day. Prx1Cre(+)/Tgfbr2(f/f) embryos showed significantly reduced cell proliferation in the developing mesenchyme of the skull by E14.5 day without any detectable alteration in apoptosis suggesting that reduced cell proliferation in Prx1Cre(+)/Tgfbr2(f/f) embryos was at least partially responsible for the defects observed. Immunofluorescent staining showed a significant reduction in the expression of Runx2/Cbfa1 and Osterix/Sp7 in Prx1Cre(+)/Tgfbr2(f/f) embryos suggesting that osteoblast differentiation was also altered in Prx1Cre(+)/Tgfbr2(f/f) embryos. To distinguish between the effects of losing Tgfbr2 on mesenchymal proliferation versus osteoblast differentiation, osteoprogenitor cells from the skulls of Tgfbr2(f/f) embryos were cultured under conditions of high cell density and Tgfbr2 was deleted from the cells using Adeno-Cre virus. RT-PCR analysis showed that the mRNA level of Runx2 and Osterix as well as Dlx5 and Msx2 were down-regulated in Tgfbr2-deleted cultures compared to control cultures indicating that Tgfbr2 regulates osteoblast differentiation independent of regulating proliferation. Together, these results suggest that Tgfbr2 is required for normal development of the skull.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1095-564X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
334
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
481-90
pubmed:dateRevised
2011-9-26
pubmed:meshHeading
pubmed-meshheading:19699732-Animals, pubmed-meshheading:19699732-Cell Differentiation, pubmed-meshheading:19699732-Cell Division, pubmed-meshheading:19699732-Core Binding Factor Alpha 1 Subunit, pubmed-meshheading:19699732-Embryo Culture Techniques, pubmed-meshheading:19699732-Frontal Bone, pubmed-meshheading:19699732-Gene Expression Regulation, Developmental, pubmed-meshheading:19699732-Gene Knockdown Techniques, pubmed-meshheading:19699732-Genes, Lethal, pubmed-meshheading:19699732-Homeodomain Proteins, pubmed-meshheading:19699732-Mesoderm, pubmed-meshheading:19699732-Mice, pubmed-meshheading:19699732-Mice, Transgenic, pubmed-meshheading:19699732-Osteoblasts, pubmed-meshheading:19699732-Osteogenesis, pubmed-meshheading:19699732-Parietal Bone, pubmed-meshheading:19699732-Protein-Serine-Threonine Kinases, pubmed-meshheading:19699732-Receptors, Transforming Growth Factor beta, pubmed-meshheading:19699732-Transcription Factors
pubmed:year
2009
pubmed:articleTitle
Tgfbr2 is required for development of the skull vault.
pubmed:affiliation
Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL 35294-0005, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural