|
|
|
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
First published online 25 October 2006
doi: 10.1242/dev.02680
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Molecular, Cell and Developmental Biology, University of
California, Los Angeles, CA 90095, USA.
2 Department of Orthopaedic Surgery, David Geffen School of Medicine at the
University of California, Los Angeles, CA 90095, USA.
3 Department of Molecular Genetics, University of Texas MD Anderson Cancer
Center, Houston, TX 77030, USA.
4 Laboratory of Reproductive and Developmental Toxicology, National Institute of
Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
* Author for correspondence (e-mail: klyons{at}mednet.ucla.edu)
Accepted 22 September 2006
Bone morphogenetic protein (BMP) signaling pathways are essential regulators of chondrogenesis. However, the roles of these pathways in vivo are not well understood. Limb-culture studies have provided a number of essential insights, including the demonstration that BMP pathways are required for chondrocyte proliferation and differentiation. However, limb-culture studies have yielded contradictory results; some studies indicate that BMPs exert stimulatory effects on differentiation, whereas others support inhibitory effects. Therefore, we characterized the skeletal phenotypes of mice lacking Bmpr1a in chondrocytes (Bmpr1aCKO) and Bmpr1aCKO;Bmpr1b+/- (Bmpr1aCKO;1b+/-) in order to test the roles of BMP pathways in the growth plate in vivo. These mice reveal requirements for BMP signaling in multiple aspects of chondrogenesis. They also demonstrate that the balance between signaling outputs from BMP and fibroblast growth factor (FGF) pathways plays a crucial role in the growth plate. These studies indicate that BMP signaling is required to promote Ihh expression, and to inhibit activation of STAT and ERK1/2 MAPK, key effectors of FGF signaling. BMP pathways inhibit FGF signaling, at least in part, by inhibiting the expression of FGFR1. These results provide a genetic in vivo demonstration that the progression of chondrocytes through the growth plate is controlled by antagonistic BMP and FGF signaling pathways.
Key words: Bone morphogenetic protein, Cartilage, Chondrogenesis, Fibroblast growth factor, indian hedgehog, BMP receptors, Mouse
Related articles in Development:
This article has been cited by other articles:
|
|
 |
|
  S. Itoh, S. Kanno, Z. Gai, H. Suemoto, M. Kawakatsu, H. Tanishima, Y. Morimoto, K. Nishioka, I. Hatamura, M. Yoshida, et al. Trps1 plays a pivotal role downstream of Gdf5 signaling in promoting chondrogenesis and apoptosis of ATDC5 cells. Genes Cells, April 1, 2008; 13(4): 355 - 363. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. L. Cooper and C. J. Tabin Understanding of bat wing evolution takes flight Genes & Dev., January 15, 2008; 22(2): 121 - 124. [Full Text] [PDF]
|
|
|
|
 |
|
 J. Gouttenoire, U. Valcourt, C. Bougault, E. Aubert-Foucher, E. Arnaud, L. Giraud, and F. Mallein-Gerin Knockdown of the Intraflagellar Transport Protein IFT46 Stimulates Selective Gene Expression in Mouse Chondrocytes and Affects Early Development in Zebrafish J. Biol. Chem., October 19, 2007; 282(42): 30960 - 30973. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Nilsson, E. A Parker, A. Hegde, M. Chau, K. M Barnes, and J. Baron Gradients in bone morphogenetic protein-related gene expression across the growth plate J. Endocrinol., April 1, 2007; 193(1): 75 - 84. [Abstract] [Full Text] [PDF]
|
|
