Antagonistic effects of Smad2 versus Smad7 are sensitive to their expression level during tooth development.
Members of the transforming growth factor-beta (TGF-beta) superfamily regulate cell proliferation, differentiation, and apoptosis, controlling the development and maintenance of most tissues. TGF-beta signal is transmitted through the phosphorylation of Smad proteins by TGF-beta receptor serine/threonine kinase. During early tooth development, TGF-beta inhibits proliferation of enamel organ epithelial cells but the underlying molecular mechanisms are largely unknown. Here we tested the hypothesis that antagonistic effects between Smad2 and Smad7 regulate TGF-beta signaling during tooth development. Attenuation of Smad2 gene expression resulted in significant advancement of embryonic tooth development with increased proliferation of enamel organ epithelial cells, while attenuation of Smad7 resulted in significant inhibition of embryonic tooth development with increased apoptotic activity within enamel organ epithelium. These findings suggest that different Smads may have differential activities in regulating TGF-beta-mediated cell proliferation and death. Furthermore, functional haploinsufficiency of Smad2, but not Smad3, altered TGF-beta-mediated tooth development. The results indicate that Smads are critical factors in orchestrating TGF-beta-mediated gene regulation during embryonic tooth development. The effectiveness of TGF-beta signaling is highly sensitive to the level of Smad gene expression.
Ito
Y
Y
Center for Craniofacial Molecular Biology School of Dentistry, University of Southern California, Los Angeles, California 90033, USA.
Zhao
J
J
Mogharei
A
A
Shuler
C F
CF
Weinstein
M
M
Deng
C
C
Chai
Y
Y
D000818:Animals; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005260:Female; D015870:Gene Expression; D017403:In Situ Hybridization; D051379:Mice; D008969:Molecular Sequence Data; D009024:Morphogenesis; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D051899:Smad2 Protein; D051906:Smad7 Protein; D014070:Tooth / Q000254:growth & development*; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000502:physiology
D004268:DNA-Binding Proteins; D016376:Oligonucleotides, Antisense; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D051906:Smad7 Protein; C497807:Smad7 protein, mouse; D015534:Trans-Activators; D016212:Transforming Growth Factor beta