Inactivation of Tgfbr2 in Osterix-Cre expressing dental mesenchyme disrupts molar root formation.
It has been difficult to examine the role of TGF-ß in post-natal tooth development due to perinatal lethality in many of the signaling deficient mouse models. To address the role of Tgfbr2 in postnatal tooth development, we generated a mouse in which Tgfbr2 was deleted in odontoblast- and bone-producing mesenchyme. Osx-Cre;Tgfbr2(fl/fl) mice were generated (Tgfbr2(cko)) and post-natal tooth development was compared in Tgfbr2(cko) and control littermates. X-ray and μCT analysis showed that in Tgfbr2(cko) mice radicular dentin matrix density was reduced in the molars. Molar shape was abnormal and molar eruption was delayed in the mutant mice. Most significantly, defects in root formation, including failure of the root to elongate, were observed by postnatal day 10. Immunostaining for Keratin-14 (K14) was used to delineate Hertwig's epithelial root sheath (HERS). The results showed a delay in elongation and disorganization of the HERS in Tgfbr2(cko) mice. In addition, the HERS was maintained and the break up into epithelial rests was attenuated suggesting that Tgfbr2 acts on dental mesenchyme to indirectly regulate the formation and maintenance of the HERS. Altered odontoblast organization and reduced Dspp expression indicated that odontoblast differentiation was disrupted in the mutant mice likely contributing to the defect in root formation. Nevertheless, expression of Nfic, a key mesenchymal regulator of root development, was similar in Tgfbr2(cko) mice and controls. The number of osteoclasts in the bone surrounding the tooth was reduced and osteoblast differentiation was disrupted likely contributing to both root and eruption defects. We conclude that Tgfbr2 in dental mesenchyme and bone is required for tooth development particularly root formation.
Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Ying
Y
Wang
Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Megan K
MK
Cox
Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
George
G
Coricor
Institute of Oral Health Research, School of Dentistry, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Mary
M
MacDougall
Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Rosa
R
Serra
D000539:Alveolar Process / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002452:Cell Count; D002454:Cell Differentiation; D004848:Epithelium / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D019426:Integrases / Q000378:metabolism*; D008648:Mesoderm / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008963:Molar / Q000254:growth & development* / Q000378:metabolism / Q000473:pathology; D051839:NFI Transcription Factors / Q000378:metabolism; D009804:Odontoblasts / Q000378:metabolism / Q000473:pathology; D038081:Organogenesis; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D021381:Protein Transport; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D000076182:Sp7 Transcription Factor; D014078:Tooth Eruption; D014092:Tooth Root / Q000254:growth & development* / Q000378:metabolism / Q000473:pathology; D014157:Transcription Factors / Q000378:metabolism*
D051839:NFI Transcription Factors; C497648:Nfic protein, mouse; D018125:Receptors, Transforming Growth Factor beta; D000076182:Sp7 Transcription Factor; C479466:Sp7 protein, mouse; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; C045073:Cre recombinase; D019426:Integrases
Eruption; HERS; Odontoblast; Osteoclast