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Repulsive axonal pathfinding requires the Ena/VASP family of actin regulatory proteins in vertebrates

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dc.contributor.advisor Frank B. Gertler. en_US Van Veen, John Edward en_US
dc.contributor.other Massachusetts Institute of Technology. Dept. of Biology. en_US 2012-10-10T15:44:22Z 2012-10-10T15:44:22Z 2012 en_US 2012 en_US
dc.description Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2012. en_US
dc.description Cataloged from PDF version of thesis. en_US
dc.description Includes bibliographical references. en_US
dc.description.abstract Vertebrate nervous system development requires the careful interpretation of many attractive and repulsive guidance molecules. For the incredibly complicated wiring diagram comprising the vertebrate nervous system to elaborate properly, the highly motile "growth cone" at the tip of an axon must sense extracellular embryonic cues and respond through a number of intracellular interactions leading ultimately to coordinated changes in cytoskeletal morphology and modulation of the axonal path. Here I describe axon pathfinding defects displayed by mice genetically deficient for all three vertebrate Ena/VASP homologues: Mena, VASP, and EVL. As has been reported previously in invertebrates, these defects share phenotypic overlap with those seen in mice genetically deficient for the repulsive guidance molecules Slit and Robo. I find that the pathfinding errors observed in Ena/VASP deficient mice are likely a result of failure to respond to Slit/Robo. Furthermore, based on my findings, I propose a "four-step" model of growth cone responses to repulsive cues. Finally I find that the direct binding of Ena/VASP proteins to Robo seen in invertebrates is conserved and expanded in vertebrates. These interactions appear to be tunable by phosphorylation, suggesting a model by which context dictates the Ena/VASP:Robo interaction, potentially leading to changes in growth cone responsiveness to guidance cues. en_US
dc.description.statementofresponsibility by John Edward van Veen. en_US
dc.format.extent 148 p. en_US
dc.language.iso eng en_US
dc.publisher Massachusetts Institute of Technology en_US
dc.rights M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission. en_US
dc.rights.uri en_US
dc.subject Biology. en_US
dc.title Repulsive axonal pathfinding requires the Ena/VASP family of actin regulatory proteins in vertebrates en_US
dc.type Thesis en_US Ph.D. en_US
dc.contributor.department Massachusetts Institute of Technology. Dept. of Biology. en_US
dc.identifier.oclc 810144504 en_US

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