Collaborative Research: Calcium Channel Beta Subunits in Early Development

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Shortly after fertilization, cells of the vertebrate embryo undergo substantial movement and rearrangement. This dramatic restructuring of embryo morphology involves epiboly, a process by which the embryonic cell mass spreads over the surface of the yolk. Epiboly is followed by gastrulation, a large-scale rearrangement of tissues leading to formation of germ layers that ultimately give rise to all the organs and tissues of the body. An important focus of developmental biology research is to understand the molecular mechanisms controlling epiboly and gastrulation. Using molecular genetic approaches, Dr Garrity's and Dr Horne's laboratories recently identified the calcium channel beta subunit as essential for normal epiboly in zebrafish. Classically, the beta subunit is thought to function as a critical auxiliary subunit of voltage-gated calcium channels (VGCCs), multi-protein complexes that mediate calcium entry into the cell. The auxiliary beta subunits (beta1- beta4) help transport the pore-forming alpha1 subunit to the cell membrane and modulate the electrophysiological properties of the calcium channel. However, recent research suggests that beta subunits may have additional functions in the cell independent of their roles in VGCCs. Mutations in the beta subunit lead to uncoordinated, lethargic behavior and seizures in mice, and have been associated with epilepsy in humans. Ongoing research in Dr Garrity's and Dr Horne's laboratories will use a combination of molecular genetic and biochemical approaches to test potential roles for the beta subunit in interacting with cytoskeletal components or in cell division or differentiation. The proposed research in zebrafish is expected to define new cellular roles for the beta subunit family, which could extend to other cell types in different physiological contexts, and may lead to a better understanding of disease phenotypes in mice and humans. The research will also contribute to our basic understanding of the molecular mechanisms driving epiboly. This collaboration will provide training and research opportunities for graduate and undergraduate students on two campuses, utilizing video conferencing. It will also provide summer internship opportunities for minority undergraduate students enrolled at Colorado State University-Pueblo, an affiliated Hispanic Serving Institution.