title: TGF-beta superfamily signaling is essential for tooth and hair morphogenesis and differentiation.
abstract: Members of the transforming growth factor beta (TGF-beta) superfamily of signaling molecules are involved in the regulation of many developmental processes that involve the interaction between mesenchymal and epithelial tissues. Smad7 is a potent inhibitor of many members of the TGF-beta family, notably TGF-beta and activin. In this study, we show that embryonic overexpression of Smad7 in stratified epithelia using a keratin 5 promoter, results in severe morphogenetic defects in skin and teeth and leads to embryonic and perinatal lethality. To further analyze the functions of Smad7 in epithelial tissues of adult mice, we used an expression system that allowed a controlled overexpression of Smad7 in terms of both space and time. Skin defects in adult mice overexpressing Smad7 were characterized by hyper-proliferation and missing expression of early markers of keratinocyte differentiation. Upon Smad7-mediated blockade of TGF-beta superfamily signaling, ameloblasts failed to produce an enamel layer in incisor teeth. In addition, TGF-beta blockade in adult mice altered the pattern of thymic T cell differentiation and the number of thymic T cells was significantly reduced. This study shows that TGF-beta superfamily signaling is essential for development of hair, tooth and T-cells as well as differentiation and proliferation control in adult tissues.
authors.affiliation: I. Medical Department, Section Pathophysiology, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Borut
authors.initials: B
authors.lastname: Klopcic
authors.forename: Thorsten
authors.initials: T
authors.lastname: Maass
authors.forename: Erik
authors.initials: E
authors.lastname: Meyer
authors.forename: Hans A
authors.initials: HA
authors.lastname: Lehr
authors.forename: Daniel
authors.initials: D
authors.lastname: Metzger
authors.forename: Pierre
authors.initials: P
authors.lastname: Chambon
authors.forename: Amrit
authors.initials: A
authors.lastname: Mann
authors.forename: Manfred
authors.initials: M
authors.lastname: Blessing
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D047108:Embryonic Development; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006197:Hair / Q000002:abnormalities / Q000166:cytology* / Q000196:embryology* / Q000473:pathology; D006801:Humans; D019426:Integrases / Q000378:metabolism; D007381:Intermediate Filament Proteins / Q000378:metabolism; D007763:Lac Operon; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D011817:Rabbits; D015398:Signal Transduction; D051906:Smad7 Protein / Q000378:metabolism; D016019:Survival Analysis; D014070:Tooth / Q000166:cytology* / Q000196:embryology* / Q000473:pathology; D014071:Tooth Abnormalities / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D019076:Transgenes
chemical_list: D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D051906:Smad7 Protein; D016212:Transforming Growth Factor beta; C045073:Cre recombinase; D019426:Integrases