Erik W. Dent
Associate Professor, Department of Neuroscience
Ph.D. University of Wisconsin-Madison
Cytoskeletal Dynamics in Neuronal Morphogenesis
We are interested in understanding how the central nervous system (CNS) develops and functions at the cellular level. Nervous system structure and function is highly dependent on the cytoskeleton. In the CNS the cytoskeleton is comprised of three polymer systems: actin filaments, microtubules and neurofilaments. Our main focus is understanding how microtubules and actin filaments interact in space and time during important morphological events in neuronal development and adulthood. Our working hypothesis is that many of the same cytoskeletal dynamics that are key for neuritogenesis and axon guidance are recapitulated at later times in development, such as during dendritic spine formation/plasticity. To study these dynamic events we use several forms of high-resolution, time-lapse microscopy, including total internal reflection fluorescence microscopy (TIRFM), wide-field microscopy and confocal imaging. We have three primary areas of study in the lab. One area of study is focused on our recent discovery that microtubules in dendrites remain dynamic throughout the life of CNS neurons and specifically target small protrusions on dendrites termed spines. These spines are the sites of contact with presynaptic axons and their activity-induced morphological changes are likely to underlie memory formation. Notably, microtubule invasion of spines is regulated by neuronal activity and appears to be important for spine maintenance and plasticity. The second area of study is the study of neurite formation and its regulation by the F-BAR protein CIP4. This protein interacts with the plasma membrane and with actin-associated proteins. We recently discovered that it behaves in a context-dependent manner in neurons and non-neuronal cells. Our third area of study is to determine how neurons respond to gradients of guidance cues and how micropatterning substrates affect neurite outgrowth. To conduct these experiments we collaborate with the Williams lab in Biomedical Engineering.
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