Back to Search
Start Over
Trigenic neural crest-restricted Smad7 over-expression results in congenital craniofacial and cardiovascular defects.
- Source :
-
Developmental biology [Dev Biol] 2010 Aug 01; Vol. 344 (1), pp. 233-47. Date of Electronic Publication: 2010 May 08. - Publication Year :
- 2010
-
Abstract
- Smad7 is a negative regulator of TGFbeta superfamily signaling. Using a three-component triple transgenic system, expression of the inhibitory Smad7 was induced via doxycycline within the NCC lineages at pre- and post-migratory stages. Consistent with its role in negatively regulating both TGFbeta and BMP signaling in vitro, induction of Smad7 within the NCC significantly suppressed phosphorylation levels of both Smad1/5/8 and Smad2/3 in vivo, resulting in subsequent loss of NCC-derived craniofacial, pharyngeal and cardiac OFT cushion cells. At the cellular level, increased cell death was observed in pharyngeal arches. However, cell proliferation and NCC-derived smooth muscle differentiation were unaltered. NCC lineage mapping demonstrated that cardiac NCC emigration and initial migration were not affected, but subsequent colonization of the OFT was significantly reduced. Induction of Smad7 in post-migratory NCC resulted in interventricular septal chamber septation defects, suggesting that TGFbeta superfamily signaling is also essential for cardiac NCC at post-migratory stages to govern normal cardiac development. Taken together, the data illustrate that tightly regulated TGFbeta superfamily signaling plays an essential role during craniofacial and cardiac NCC colonization and cell survival in vivo.<br /> (Copyright (c) 2010 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Branchial Region abnormalities
Cardiovascular Diseases congenital
Cardiovascular Diseases genetics
Cell Lineage
Cell Survival
Craniofacial Abnormalities genetics
Mice
Models, Biological
Models, Genetic
Myocardium metabolism
Transcriptional Activation
Transgenes
Gene Expression Regulation
Neural Crest metabolism
Smad7 Protein genetics
Smad7 Protein physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1095-564X
- Volume :
- 344
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Developmental biology
- Publication Type :
- Academic Journal
- Accession number :
- 20457144
- Full Text :
- https://doi.org/10.1016/j.ydbio.2010.05.004