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Ectodermal Smad4 and p38 MAPK are functionally redundant in mediating TGF-beta/BMP signaling during tooth and palate development.
- Source :
-
Developmental cell [Dev Cell] 2008 Aug; Vol. 15 (2), pp. 322-9. - Publication Year :
- 2008
-
Abstract
- Smad4 is a central intracellular effector of TGF-beta signaling. Smad-independent TGF-beta pathways, such as those mediated by p38 MAPK, have been identified in cell culture systems, but their in vivo functional mechanisms remain unclear. In this study, we investigated the role of TGF-beta signaling in tooth and palate development and noted that conditional inactivation of Smad4 in oral epithelium results in much milder phenotypes than those seen with the corresponding receptor mutants, Bmpr1a and Tgfbr2, respectively. Perturbed p38 function in these tissues likewise has no effect by itself; however, when both Smad4 and p38 functions are compromised, dramatic recapitulation of the receptor mutant phenotypes results. Thus, our study demonstrates that p38 and Smad4 are functionally redundant in mediating TGF-beta signaling in diverse contexts during embryonic organogenesis. The ability of epithelium to utilize both pathways illustrates the complicated nature of TGF-beta signaling mechanisms in development and disease.
- Subjects :
- Animals
Body Patterning
Enzyme Activation
Epithelium embryology
Epithelium metabolism
Female
Gene Expression Regulation, Developmental
In Situ Hybridization
Integrases metabolism
Male
Mice
Mutation genetics
Palate enzymology
Signal Transduction
Tooth enzymology
Tooth Abnormalities
Tooth Germ embryology
Tooth Germ metabolism
Bone Morphogenetic Proteins metabolism
Ectoderm enzymology
Palate embryology
Smad4 Protein metabolism
Tooth embryology
Transforming Growth Factor beta metabolism
p38 Mitogen-Activated Protein Kinases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1878-1551
- Volume :
- 15
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Developmental cell
- Publication Type :
- Academic Journal
- Accession number :
- 18694570
- Full Text :
- https://doi.org/10.1016/j.devcel.2008.06.004