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Developmental Genetics and Cell Biology

Directed changes in the shape of epithelial sheets are required to create many of the major tissues in animals, including the intestinal system, kidneys, lungs, and skin. Although our understanding of epithelial sheet morphogenesis has advanced in recent years, we still have much to learn about this fundamental developmental process. Research in my laboratory focuses on understanding at a cellular and molecular level the mechanisms by which epithelial sheets change shape during their development. I have chosen to study epithelial shape change in the model system C. elegans because it occurs in a simple, predictable fashion, allowing us to characterize this process at a genetic, cellular and organismal level. During C. elegans embryogenesis, epithelial cells elongate over four-fold, driven by dramatic changes in the organization of all major cytoskeletal structures. Because the forces that drive cell shape change act on the apical membrane skeleton of epithelial cells, this structure must be both strong and dynamic. One protein that localizes to the apical membrane skeleton and is required for epithelial cell shape change is SMA-1 spectrin, an ortholog of Drosophila H-spectrin and human V-spectrin. sma-1 mutants fail to elongate properly during embryogenesis. Our analysis of sma-1mutants has shown that SMA-1 has two discreet functions in epithelial elongation: to maintain the association of actin at the apical membrane and to preserve changes in the organization of the apical membrane. Ongoing research aims to better understand these roles for SMA-1 spectrin and to identify the proteins that interact with SMA-1 in epithelial morphogenesis. As a result of these studies, we will gain fundamental insights into how changes in the apical membrane skeleton contribute to epithelial cell elongation, a process fundamental to the development of all animals.