Smad1 expression and function during mouse embryonic lung branching morphogenesis

被引:24
作者
Chen, C
Chen, H
Sun, JP
Bringas, P
Chen, YH
Warburton, D
Shi, W
机构
[1] Childrens Hosp Los Angeles, Dept Surg, Dev Biol Program, Saban Res Inst, Los Angeles, CA 90027 USA
[2] Univ So Calif, Ctr Craniofacial Mol Biol, Los Angeles, CA USA
[3] China Med Univ, Dept Dev Biol, Shenyang, Peoples R China
关键词
lung development; bone morphogenetic protein 4;
D O I
10.1152/ajplung.00277.2004
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Bone morphogenetic protein ( BMP) 4 plays very important roles in regulating developmental processes of many organs, including lung. Smad1 is one of the BMP receptor downstream signaling proteins that transduce BMP4 ligand signaling from cell surface to nucleus. The dynamic expression patterns of Smad1 in embryonic mouse lungs were examined using immunohistochemistry. Smad1 protein was predominantly detected in peripheral airway epithelial cells of early embryonic lung tissue [ embryonic day 12.5 (E12.5)], whereas Smad1 protein expression in mesenchymal cells increased during mid- late gestation. Many Smad1- positive mesenchymal cells were localized adjacent to large airway epithelial cells and endothelial cells of blood vessels, which colocalized with a molecular marker of smooth muscle cells (alpha-smooth muscle actin). The biological function of Smad1 in early lung branching morphogenesis was then studied in our established E11.5 lung explant culture model. Reduction of endogenous Smad1 expression was achieved by adding a Smad1-specific antisense DNA oligonucleotide, causing similar to 20% reduction of lung epithelial branching. Furthermore, airway epithelial cell proliferation and differentiation were also inhibited when endogenous Smad1 expression was knocked down. Therefore, these data indicate that Smad1, acting as an intracellular BMP signaling pathway component, positively regulates early mouse embryonic lung branching morphogenesis.
引用
收藏
页码:L1033 / L1039
页数:7
相关论文
共 30 条
[1]  
Bellusci S, 1996, DEVELOPMENT, V122, P1693
[2]   Signaling to the epithelium is not sufficient to mediate all of the effects of transforming growth factor β and bone morphogenetic protein 4 on murine embryonic lung development [J].
Bragg, AD ;
Moses, HL ;
Serra, R .
MECHANISMS OF DEVELOPMENT, 2001, 109 (01) :13-26
[3]   Smad5 is essential for left-right asymmetry in mice [J].
Chang, H ;
Zwijsen, A ;
Vogel, H ;
Huylebroeck, D ;
Matzuk, MM .
DEVELOPMENTAL BIOLOGY, 2000, 219 (01) :71-78
[4]  
Chang H, 1999, DEVELOPMENT, V126, P1631
[5]   Smad-dependent and Smad-independent pathways in TGF-β family signalling [J].
Derynck, R ;
Zhang, YE .
NATURE, 2003, 425 (6958) :577-584
[6]  
Dick A, 1998, DEV DYNAM, V211, P293, DOI 10.1002/(SICI)1097-0177(199804)211:4<293::AID-AJA1>3.0.CO
[7]  
2-C
[8]  
Hogan BLM, 1997, COLD SPRING HARB SYM, V62, P249
[9]   Bone morphogenetic proteins in development [J].
Hogan, BLM .
CURRENT OPINION IN GENETICS & DEVELOPMENT, 1996, 6 (04) :432-438
[10]   Morphogenesis [J].
Hogan, BLM .
CELL, 1999, 96 (02) :225-233