Abstract

Bone morphogenetic proteins (BMP) are members of the transforming growth factor-b (TGF-b) family of cytokines that play a variety of different roles during animal development. Although BMPs were first identified for their bone-inducing abilities, surprisingly there is currently no in vivo evidence for a general requirement for BMP signaling in skeleton formation. Standard mouse knockouts for genes encoding BMP signaling proteins have not been very informative because many die during early embryogenesis before skeleton formation. We have performed conditional genetic studies and provide evidence that BMP type I receptors are essential and act redundantly for skeleton formation, thus revealing BMP signaling complexity. In combination with transgenic mice that express cre recombinase in limb mesenchyme and chondrocytes, we propose to examine the requirement and complexity of BMP signaling proteins in skeletal development.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Program Projects (P01)
Project #
2P01AR042919-09
Application #
6786526
Study Section
Special Emphasis Panel (ZAR1-TEN-A (J2))
Project Start
2004-04-01
Project End
2005-05-31
Budget Start
2004-04-01
Budget End
2005-05-31
Support Year
9
Fiscal Year
2004
Total Cost
$213,041
Indirect Cost

  Institution

Name
University of Texas MD Anderson Cancer Center
Department
Type
DUNS #
800772139
City
Houston
State
TX
Country
United States
Zip Code
77030

  Publications

Coustry, Francoise; Oh, Chun-do; Hattori, Takako et al. (2010) The dimerization domain of SOX9 is required for transcription activation of a chondrocyte-specific chromatin DNA template. Nucleic Acids Res 38:6018-28
Nuka, S; Zhou, W; Henry, S P et al. (2010) Phenotypic characterization of epiphycan-deficient and epiphycan/biglycan double-deficient mice. Osteoarthritis Cartilage 18:88-96
Hattori, Takako; Coustry, Francoise; Stephens, Shelley et al. (2008) Transcriptional regulation of chondrogenesis by coactivator Tip60 via chromatin association with Sox9 and Sox5. Nucleic Acids Res 36:3011-24
Lee, Hu-Hui; Behringer, Richard R (2007) Conditional expression of Wnt4 during chondrogenesis leads to dwarfism in mice. PLoS One 2:e450
Govoni, Kristen E; Lee, Seong Keun; Chung, Yoon-Sok et al. (2007) Disruption of insulin-like growth factor-I expression in type IIalphaI collagen-expressing cells reduces bone length and width in mice. Physiol Genomics 30:354-62
Gebhard, Sonja; Hattori, Takako; Bauer, Eva et al. (2007) BAC constructs in transgenic reporter mouse lines control efficient and specific LacZ expression in hypertrophic chondrocytes under the complete Col10a1 promoter. Histochem Cell Biol 127:183-94
Kimura, Hiroaki; Akiyama, Haruhiko; Nakamura, Takashi et al. (2007) Tenascin-W inhibits proliferation and differentiation of preosteoblasts during endochondral bone formation. Biochem Biophys Res Commun 356:935-41
Akiyama, Haruhiko; Stadler, H Scott; Martin, James F et al. (2007) Misexpression of Sox9 in mouse limb bud mesenchyme induces polydactyly and rescues hypodactyly mice. Matrix Biol 26:224-33
Ovchinnikov, Dmitry A; Selever, Jennifer; Wang, Ying et al. (2006) BMP receptor type IA in limb bud mesenchyme regulates distal outgrowth and patterning. Dev Biol 295:103-15
Steiglitz, Barry M; Kreider, Jaclynn M; Frankenburg, Elizabeth P et al. (2006) Procollagen C proteinase enhancer 1 genes are important determinants of the mechanical properties and geometry of bone and the ultrastructure of connective tissues. Mol Cell Biol 26:238-49

Showing the most recent 10 out of 64 publications