NSF Award
9506156
9506156 Gossler Somitogenesis is a fundamental pattern forming process in vertebrates that subdivides the paraxial mesoderm along the anterior-posterior body axis into a series of homologous subunits called somites. The somites acquire distinct identities according to their axial position and during subsequent differentiation, they give rise to specific anatomical structures along the anterior posterior body axis. The molecular mechanisms that control the formation of somites from the presomitic (unsegmented) mesoderm remain to be elucidated. Mouse mutations that specifically perturb normal somite formation and consequently lead to severe malformations of the axial skeleton indicate that different genetic elements control distinct aspects of somitogenesis, such as the formation of individual somites, or their size and shape. To understand the molecular mechanisms underlying somitogenesis and thus controlling the generation of the segmented mesodermal body parts, the isolation and functional characterization of genes involved in the regulation of these processes are essential. In this proposal Dr. Gossler will focus on the functional analysis in vivo of a recently isolated mouse gene Dll1 (delta like gene 1). Dll1 is closely related to the Drosophila Delta gene which is required for various cell fate decisions during fly development. Dll1 is transiently expressed during embryogenesis and expression is closely correlated with somitogenesis. The expression pattern and homology to Drosophila Delta strongly suggest a role for Dll1 in cell to cell interactions underling somitogenesis. To test this hypothesis Dr. Gossler will generate a null allele of Dll1 by homologous recombination in ES cells and study the consequences of this mutation during embryogenesis. To address the consequences of a mutation in Dll1 on the cellular level he will assess the developmental potential of cells carrying this mutation in chimeric embryos. Finally, he will determine the expressio n of the Dll1 gene and the distribution of its product in embryos that carry mutations affecting somitogenesis in comparison with wild type embryos. ***
