Colleen Guerin
2009-present Ph.D. Rutgers University Funded by the UNC Developmental Biology Training Program |
Regulators of the actin cytoskeleton
during morphogenesis and metastasis
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Cell protrusions are a hallmark feature of migrating cells during development and disease. During metastasis, cancer cells extend cell protrusions, become motile, and invade surrounding tissues. Cell protrusions are also required for cell migration during morphogenesis. As cells are specified during development, they must assume the correct position within the organism. Epithelial morphogenesis in the fruit fly, Drosophila melanogaster, provides an excellent model system for identifying regulators of cell protrusions. During dorsal closure, the sheet of epidermal cells migrates dorsally and encases the embryo. At the leading edge of migrating epidermal cells are highly dynamic cell protrusions. These protrusions are composed of both filopodia and lamellipodia, and previous studies in our lab discovered that a balance between these types of protrusions is necessary for proper morphogenesis. Two actin regulators, Diaphanous (Dia) and Enabled (Ena), are important modulators of cell protrusions at the leading edge during dorsal closure. Dia and Ena also play a role in cancer cell protrusions, which are required for metastasis. The roles of Dia and Ena in cancer protrusive behavior suggests cancer cells employ developmental signaling pathways and cytoskeletal machinery to drive migration and invasion. Therefore, understanding how Dia, Ena, and actin are regulated to promote cell protrusions during development will provide insight into how cancer cells acquire and regulate their migratory and invasive abilities. |
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Our preliminary studies found that Dia and Ena bind each other and regulate the type of cell protrusions formed by migrating epithelial cells in Drosophila. Therefore, I hypothesize that determining the nature and function of this interaction and identifying additional molecules that regulate Dia and Ena localization and activation will provide mechanistic insight into how cell protrusions are regulated. I will determine how Diaphanous and Enabled binding is mediated, how it affects actin dynamics at the filament level, and the role it plays in cell protrusions in vivo. I am also identifying regulators of Dia and Ena localization and activation to build a mechanistic view of cell protrusion formation. |
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Publications Guerin, C.M. and Kramer, S.G. (2009). RacGAP50C directs perinucleargamma-tubulin localization to organize the uniform microtubule array required for Drosophila myotube extension. Development, 136, 1411-1421.
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