The vertebrate skeleton is almost entirely mesodermal in origin, aside from several bones in the skull which are derived from neural crest (Noden, 1992; Couly et al., 1993). In Drosophila one of the principal genes controlling mesoderm differentiation is the bagpipe homeobox gene (Azpiazu and Frasch, 1993; Azpiazu et al., 1996). We have previously isolated from mouse and human, homologues of bagpipe termed Bapx1. Examination of the expression of Bapx1 during embryogenesis revealed an expression almost exclusively restricted to paraxial and lateral plate mesoderm, with earliest expression detectable in the presclerotome cells of the somite (Tribioli et al., 1997; Tribioli and Lufkin, 1997). During subsequent stages of embryogenesis, Bapx1 is expressed in essentially all cartilaginous condensations which will subsequently undergo endochondral ossification. To investigate the role of Bapx1 in embryonic skeletogenesis, this proposal focuses primarily on loss-of-function (gene knockout) and gain-of-function studies in vitro and in vivo. Preliminary results from mice lacking Bapx1 indicate that it plays an essential role in chondroblast differentiation within the axial skeleton, which in turn leads to failed endochondral ossification.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR046471-05
Application #
6721539
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Program Officer
Sharrock, William J
Project Start
2000-02-16
Project End
2005-01-31
Budget Start
2004-02-01
Budget End
2005-01-31
Support Year
5
Fiscal Year
2004
Total Cost
$352,670
Indirect Cost
Name
Mount Sinai School of Medicine
Department
Biology
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
Chatterjee, Sumantra; Sivakamasundari, V; Kraus, Petra et al. (2015) Gene expression profiles of Bapx1 expressing FACS sorted cells from wildtype and Bapx1-EGFP null mouse embryos. Genom Data 5:103-105
Sivakamasundari, V; Lufkin, Thomas (2013) Stemming the Degeneration: IVD Stem Cells and Stem Cell Regenerative Therapy for Degenerative Disc Disease. Adv Stem Cells 2013:
Sivakamasundari, V; Lufkin, Thomas (2012) Bridging the Gap: Understanding Embryonic Intervertebral Disc Development. Cell Dev Biol 1:
Chatterjee, Sumantra; Sivakamasundari, V; Lee, Wenqing Jean et al. (2012) Making no bones about it: Transcription factors in vertebrate skeletogenesis and disease. Trends Dev Biol 6:45-52
Ng, Patricia Miang-Lon; Lufkin, Thomas (2011) Embryonic stem cells: protein interaction networks. Biomol Concepts 2:13-25
Tribioli, Carla; Lufkin, Thomas (2006) Long-term room temperature storage of high-quality embryonic stem cell genomic DNA extracted with a simple and rapid procedure. J Biomol Tech 17:249-51
Tribioli, Carla; Lufkin, Thomas (2006) Bapx1 homeobox gene gain-of-function mice show preaxial polydactyly and activated Shh signaling in the developing limb. Dev Dyn 235:2483-92
Wang, Weidong; Grimmer, J Fredrik; Van De Water, Thomas R et al. (2004) Hmx2 and Hmx3 homeobox genes direct development of the murine inner ear and hypothalamus and can be functionally replaced by Drosophila Hmx. Dev Cell 7:439-53
Simon, Ruth; Lufkin, Thomas (2003) Postnatal lethality in mice lacking the Sax2 homeobox gene homologous to Drosophila S59/slouch: evidence for positive and negative autoregulation. Mol Cell Biol 23:9046-60