Erik W. Dent, PhD
Position title: Professor, Neuroscience
Contact Information
Department of Neuroscience
332 SMI
1300 University Ave
Madison, WI 53706
608.262.4672
ewdent@wisc.edu
Lab Website: Dent Lab
Research Statement
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, such as total internal reflection fluorescence microscopy (TIRFM), wide-field microscopy and confocal imaging. We have recently discovered that microtubules 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 may be important for spine maintenance and plasticity. We are currently studying cytoskeletal dynamics in both developing and adult mouse CNS tissue, utilizing transfected hippocampal neurons in culture and in hippocampal slices. We are also collaborating with groups in both Biomedical Engineering and Physics to determine how neurons respond to gradients of guidance cue and how micropatterning substrates affects neurite outgrowth.
Selected Publications
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Nichol, R. H., IV, Hagen, K. M., Lumbard, D. C., Dent, E. W., & Gómez, T. M. (2016). Guidance of Axons by Local Coupling of Retrograde Flow to Point Contact Adhesions. The Journal of neuroscience : the official journal of the Society for Neuroscience, 36(7), 2267–2282. https://doi.org/10.1523/JNEUROSCI.2645-15.2016
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McVicker DP, Millette MM, Dent EW. (2015) Signaling to the microtubule cytoskeleton: an unconventional role for CaMKII. Developmental Neurobiology. 75(4):423-34. doi: 10.1002/dneu.22227.
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Kalil K, Dent EW. (2014) Branch management: mechanisms of axon branching in the developing vertebrate CNS. Nature Reviews Neuroscience. 15(1):7-18. doi: 10.1038/nrn3650.
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Cavallo F, Huang Y, Dent EW, Williams JC, Lagally MG. (2014) Neurite guidance and three-dimensional confinement via compliant semiconductor scaffolds. ACS Nano. 23;8(12):12219-27. doi: 10.1021/nn503989c.
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Li L, Fothergill T, Hutchins BI, Dent EW, Kalil K. (2014) Wnt5a evokes cortical axon outgrowth and repulsive guidance by tau mediated reorganization of dynamic microtubules. Developmental Neurobiology. 74(8):797-817. doi: 10.1002/dneu.22102.
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Dent EW, Baas PW. (2014) Microtubules in neurons as information carriers. Journal of Neurochemistry. 129(2):235-9. doi: 10.1111/jnc.12621.
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Saengsawang W, Taylor KL, Lumbard DC, Mitok K, Price A, Pietila L, Gomez TM, Dent EW. (2013) CIP4 coordinates with phospholipids and actin-associated proteins to localize to the protruding edge and produce actin ribs and veils. Journal of Cell Science. Jun 1;126(Pt 11):2411-23.
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Merriam EB, Millette M, Lumbard DC, Saengsawang W, Fothergill T, Hu X, Ferhat L, Dent EW. (2013) Synaptic regulation of microtubule dynamics in dendritic spines by calcium, F-actin, and drebrin. Journal of Neuroscience. 33(42):16471-82. doi: 10.1523/JNEUROSCI.0661-13.2013.
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Hart SR, Huang Y, Fothergill T, Lumbard DC, Dent EW, Williams JC. (2013) Adhesive micro-line periodicity determines guidance of axonal outgrowth. Lab Chip. Feb 21;13(4):562-9.
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Saengsawang W, Mitok K, Viesselmann C, Pietila L, Lumbard DC, Corey SJ, Dent EW. (2012) The F-BAR protein CIP4 inhibits neurite formation by producing lamellipodial protrusions. Current Biology. Mar 20;22(6):494-501.
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Merriam EB, Lumbard DC, Viesselmann C, Ballweg J, Stevenson M, Pietila L, Hu X, Dent EW. (2011) Dynamic microtubules promote synaptic NMDA receptor-dependent spine enlargement. PLoS One . 6(11):e27688.