FUNCTIONAL STUDIES OF THE MURINE BAPX1 HOMEOBOX GENE REVEAL EMBRYONIC SKELETAL DEVELOPMENT

The aim of our project is to understand the molecular mechanisms controlling the embryonic development and to characterize the specific role of genes during embryonic patterning. There are three main reasons why the functional study of genes involved in embryonic development is important. First, it is necessary for the recognition and prevention of human defects early in pregnancy. Up to 3% of newborn infants display a major malformation. Secondly, it is necessary for the understanding of the biological mechanisms underlying normal development. Thirdly, it reveals the fact that genes work in hierarchies, and shows the genetic cascades generated by the interaction of regulatory genes. Our genetic approach is focused on studies in animals (transgenic and knockout mice), since this is the only system which permits an accurate analysis of the complex genetic interactions which occur during embryonic development. Because many of the genes controlling embryonic development have been structurally and functionally conserved during evolution and because the morphogenesis of many of the organs and tissues is evolutionary conserved, we believe that the results derived from our mouse embryo studies may ultimately aid in the prevention, detection and treatment of human birth defects. Our study is concerned Bapx1 homeobox gene. Over the past two years we have produced mutant mice carrying a Bapx1 loss-of-function mutation. By observations of the phenotypic appearance of lethal skeletal defects in homozygous mice lacking Bapx1, we provided evidence that Bapx1 gene plays a critical role early in the development of the skeleton. To complete our study here we propose to generate and study mutant mice in which Bapx1 gene expression is perturbed in defined regions in the embryo.