The long term goal of this program is to understand the molecular mechanisms controlling chondrogenic differentiation and skeletogenesis and to characterize the genes involved in embryonic skeletal patterning with the belief that such basic knowledge will give us a fundamental understanding of the developmental control of skeletogenesis.
In Drosophila, certain of the major mesodermal lineages are specified by the bagpipe homeobox gene, which is a DNA-binding transcriptional regulator. We have recently isolated from mouse a homologue of the bagpipe gene designated Bapx1. We have mapped murine Bapx1 to the proximal end of mouse chromosome 5. Bapxl encodes a predicted protein of 333 amino acids and expression of Bapx1 RNA is first detectable in E8.0 embryos in the mesoderm of themost newly formed somites in the group of cells corresponding to the presclerotome, the precursor of the vertebrae. Thus Bapx1 is one of the earliest developmental markers for the sclerotome portion of the somite. Bapx1 continues to be expressed well into organogenesis in essentially all cartilaginous condensations which will subsequently undergo endochondral bone formation of the axial, appendicular and facial skeleton. The expression pattern of Bapx1 suggests that there are evolutionary conserved mechanisms of mesoderm specification and differentiation and that the mammalian Bapx1 gene has likely acquired an important developmental role in chondrogenesis and skeletal patterning.
To investigate the developmental role of the Bapx1 gene, we will undertake the following specific aims: (I) To complete the characterization of the genomic organization, chromosomal localization, and embryonic expression pattern of the Bapx1 homeobox gene in mouse. (II) To investigate the developmental role of the Bapx1 gene in chondrogenesis and embryonic skeletal patterning, by generating a loss-of-function null mutation (gene knockout) of the Bapx1 gene in mice.
