Erik Dent

Research Interests
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, such as total internal reflection fluorescence microscopy (TIRFM), wide-field microscopy and confocal imaging. We have recently discovered 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 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 cues and how micropatterning substrates affect neurite outgrowth.

Model of f-actin and microtubule dynamics in dendritic spines(Figure – right – click to enlarge)
(a) Model of a dendritic spine showing the possible arrangement of actin filaments in the spine head, neck and dendritic shaft. Actin takes the form of short filaments with several of the filaments having their barbed (fast growing) ends near the membrane. (b) Image of a dendrite from a hippocampal neurons transfected with DsRed and EGFP-tubulin (DIV18). (c) Time-lapse images of the spine demarcated by the box in (b). DsRed label shows the morphology of the spine, while EGFP-tubulin labels microtubules. One dynamic microtubule extends into and retracts from the spine over a period of 40 seconds. (d) Model showing how a microtubule polymerizes into and retracts from a dendritic spine (see Dent et al., (2011) Current Opinions in Neurobiology, 21:175-81 for details).

Selected Publications

(^T = Technician, ^U = Undergraduate Student, ^G = Graduate Student, ^P = Postdoctoral Fellow in my lab)

• McVicker, D.P.^P, M.M. Millette^G and E.W. Dent (2015) Signaling to the microtubule cytoskeleton: An unconventional role for CaMKII. Developmental Neurobiology. 75:423-34. PMCID: PMC4340821.
• Li, L.*, T. Fothergill^P*, B.I. Hutchins, E.W. Dent and K. Kalil (2014) Wnt5a evokes cortical axon outgrowth and repulsive guidance by tau mediated reorganization of dynamic microtubules. (* equal contributions) Dev Neurobiology. 74:797-817. PMCID: PMC4087151.
• Kalil, K. and E.W. Dent (2014) Branch management: mechanisms of axon branching in the developing vertebrate CNS. Nature Reviews Neuroscience, 15:7-18. PMCID: PMC4063290.
• Cavallo, F., Y. Huang, E.W. Dent, J.C. Williams and M.G. Legally (2014) Neurite guidance and three-dimensional confinement via compliant semiconductor scaffolds. ACS Nano, 8:12219-27.
• Merriam, E.B^G., M. Millette^G, D.C. Lumbard^T, W. Saengsawang^P, T. Fothergill^P, X. Hu^G, L. Ferhat and E.W. Dent (2013) Synaptic regulation of microtubule dynamics in dendritic spines by calcium, F-actin and drebrin. J Neuroscience, 33: 16471-16482. PMCID:PMC3797370.
• Saengsawang, W^P., K.L. Taylor^G, D.C. Lumbard^T, K. Mitok^U, A. Price^U, L. Pietila^U, T.M. Gomez and E.W. Dent (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, 126:2411-2423. PMCID:PMC3679485.
• Beetz, C., A. Johnson, A.L. Schuh, S. Thakur, R-E Varga, T. Fothergill^P, N. Hertel, E. Bomba-Warczak, H. Thiele, G. Nurnberg, J. Altmuller, R. Saxena, E.R. Chapman, E.W. Dent, P. Nurnberg ad A. Audhya (2013) Inhibition of TFG function causes hereditary axon degeneration by impairing ER structure. PNAS, 110:5091-5096. PMCID: PMC3612678.
• Hart, S.R., Y. Huang, T. Fothergill^P, D.C. Lumbard^T, E.W. Dent and J.C. Williams (2013) Adhesive micro-line periodicity determines guidance of axonal growth. Lab on a Chip, 13:562-569. PMCID: PMC4123686.
• Saengsawang, W.^P, K. Mitok^U, C. Viesselmann^U, L. Pietila^U, D. Lumbard^U, S.J. Corey and E.W. Dent (2012) The F-BAR protein CIP4 inhibits neurite formation by producing lamellipodial protrusions. Current Biology, 22:494-501. PMCID: PMC3311763
• Merriam, E.B.^G, D.C Lumbard^U, C. Viesselmann^U, J. Ballweg^U, M. Stevenson^U, L. Pietila^U, X.G. Hu^G and E.W. Dent (2011) Dynamic microtubules promote NMDA receptor-dependent spine enlargement. PLoS One, 6(11); e27688.doi:10.1371/journal.pone.0027688. PMCID: PMC3214068
• Hu, X.G.^G, L. Ballo^U, L. Pietila^U, C. Viesselmann^U, J. Ballweg^U, D. Lumbard^U, M. Stevenson^U, E. Merriam^G and E.W. Dent (2011) BDNF-induced increase of PSD-95 in dendritic spines requires dynamic microtubule invasions. J Neuroscience, 31:15597-603. PMCID: PMC3224154