Mechanosensitive Regulation of Axon Guidance

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The usefulness of any model experimental system depends on the extent to which it is able to mimic normal in vivo responses. A case in point is models that use controlled tissue culture environments to investigate how neurons grow. Most researchers fail to account for all key influences that neurons encounter in the embryo, particularly the mechanical behavior of embryonic tissue. This omission turns out to be critical. Evidence from the P.I.'s laboratory shows that unless the tissue culture environment mimics the mechanical status of the embryo, certain neurons are unable to respond normally to critical guidance cues. Very little is known about how mechanical signals impact neuronal responses to molecular guidance cues. These experiments address that deficit using a tissue culture model developed by the P.I. to account for the mechanical status of the embryo. They focus on a protein that plays a key regulatory role in how neurons respond to both mechanical and molecular signals. With the aim of unraveling mechanisms that coordinate neuronal responses to molecular guidance cues in the embryo, these investigators will use biochemical and molecular approaches to manipulate the mechanical environment. Their ultimate goal is to construct a tissue culture model with maximum in vivo relevance to both neurons and other mechanosensitive cells. The work has broader impact by virtue of two K-12 outreach programs established by the P.I. The first has sponsored over 200 inner city students to perform inquiry-based projects in research laboratories. The second has established professional development for their teachers. This award will expand opportunities for both students and their teachers to participate in authentic inquiry-based research, reinforcing the STEM educational pipeline.