Cell-cell fusion is a key process in reproduction and in the morphogenesis of many multicellular organisms. However, because of the limitations of approaches used to study cell fusion, little is known about the molecular basis of the event. In the laboratory of John White at the University of Wisconsin, Madison, I propose to study the process of cell fusion in the nematode Caenorhabditis elegans. This model system offers the most tractable strategy for the study of fusion via genetic analysis and direct, detailed observation and manipulation. Information gained from this work should be readily transferred, by virtue of evolutionary conservation of both the mechanisms and genes involved, to an understanding of cell-cell fusion and the formation of various syncytial tissues of other species, including humans. Two separate directed approaches will be applied to the study of fusion in C. elegans. 1. Genes which are essential to the process of cell membrane fusion will be isolated by screening for mutants with specific deficits in cell fusion of the syncytial epidermis of C. elegans. Mapping and cloning of these genes by standard methods of C. elegans genetics will lead to identification of the molecules which direct fusion in the worm, and eventually lead to the identification of homologues in other species. 2. Individual cell-fusion events will be observed in live animals using established techniques for microscopy and the labeling of single cells in C. elegans embryos. This approach will be the basis for detailed descriptions of the structural nature and biochemical requirements of cell fusion.
