Abstract

The chondrocyte is a phenotypically heterogenous cell type suggesting that multiple molecular determinants control its differentiation. We are interested in identifying transcription regulators of chondrocyte differentiation. In particular we are interested in the role of Cbfa proteins, that are known to act as cell differentiation factors in several lineages, during this process. We have shown previously that Cbfa1 is expressed early during development in a common progenitor for chondrogenic zones, however, its role during chondrocyte differentiation could not be analyzed because of the early lethality of Cbfa-deficient embryos. We propose here to perform a systematic analysis of Cbfa2 expression pattern during chondrogenesis and to use genetic means to decipher its role in this process by deleting or over-expressing this gene only in chondrocytes.
The specific aims are: To perform a complete and comparative study of the pattern of expression of Cbfa and Cbfa1 by in situ hybridization and immunocytochemistry. To generate and study the phenotype of chondrocyte-specific Cbfa2- deficient mice. To generate transgenic mice expressing permanently Cbfa1 in chondrocytic cells and to analyze their phenotype. To study any cross regulation between Cbfa2 and Cbfa1.

  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 #
5P01AR042919-06
Application #
6443311
Study Section
Project Start
2001-04-01
Project End
2002-03-31
Budget Start
Budget End
Support Year
6
Fiscal Year
2001
Total Cost
$188,233
Indirect Cost

  Institution

Name
University of Texas MD Anderson Cancer Center
Department
Type
DUNS #
001910777
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