Regulation of Functionally-distinct Adhesions and Neuronal Motility

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Nervous system function depends critically on the formation of appropriate connections during development. To accomplish this task, neurons extend axons that navigate using a dynamic structure at their tips, the growth cone. Growth cones do not swim though the embryo: they crawl along sticky surfaces and advance only by making adhesions. A crucial advance toward understanding these adhesions comes from members of the Tosney lab, who discovered that all adhesions are not equivalent. Instead, two distinct types of adhesions regulate two different motile structures: "filopodia" that act as a tiny antennae-like sensors, and "veils" that spread the growth cone forward. Cues in the embryo can guide growth cones by controlling these special adhesions, which in turn control the filopodia and veils. This project will test the hypothesis that these adhesions are regulated by different molecular signals. Researchers will experimentally perturb signals while directly observing labeled molecular components, adhesions and motile structures in live growth cones. Since similar adhesions are crucial components of all moving cells, these studies are key for understanding the movement of multiple cell types, including cells that build the organism during development and cells that endanger the organism during metastasis. In addition to advancing understanding, the project directly promotes training of graduate, undergraduate and high school students, including those of underrepresented groups. For instance, the PI has already trained three dozen undergraduates in research. Many wrote honors theses, presented their work at interdisciplinary professional meetings, coauthored publications, and advanced to professional training. In addition to disseminating findings in the usual venues of publications and meetings, the PI directs the Society for Developmental Biology Education Website which synthesizes education materials for public presentation. The proposed research project will sustain the mentoring and training of diverse student researchers at multiple levels, as well as the dissemination of research findings and philosophies to wide audiences.