The nematode Caenorhabditis elegans will be used as a model system to study cell fate specification during development. This research is focused on addressing how choices between different mesodermal fates are made. In higher eukaryotes, patterning of mesoderm is essential for proper development, since these cells contribute to blood, organs, and connective tissues. This process involves the complex interplay of cell intrinsic and extrinsic factors so that the different tissue types are formed at the correct time and in the correct place. Failure to properly specify mesodermal fates can lead to severe developmental defects or death. Since the genome is sequenced and since lineage of all somatic cells of C. elegans are known, this system allows for the rapid characterization of gene activities at a cellular level. Two approaches will be used to address questions of mesodermal patterning. First, genetic screens will be performed to isolate mutations which alter the specification of mesodermal cells called coelomocytes. These cells provide an excellent opportunity to studying non-muscle mesodermal fates since they arise from three different parts of the lineage and they are born very late during embryogenesis. Defects in coelomocyte specification will be assayed using tissue specific markers. The mutations and corresponding genes will be characterized using standard genetic and molecular techniques. Gene function will be characterized using laser ablations, mosaic analyses, and expression studies. Second, embryo manipulation experiments, i.e. laser ablations, will be performed to determine the relative contributions of cell intrinsic cues and inductive signals. These studies are expected to provide insight into the basic mechanisms of cell fate specification during development. In addition, since many of the molecules involved in similar processes are known to be activated in cancer cells, this work may increase our understanding of tumor formation and metastasis.
