Cytoskeletal Dynamics in Neuronal Morphogenesis
Office Phone: (608) 262-4672
Research Strength: Development: Plasticity and Repair
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.
- Staii, C., C. Viesselmann, J. Ballweg, L. Shi, G-Y. Liu, J. Williams, E.W. Dent, S.N. Coopersmith, and M.A. Eriksson. 2009. Positioning and guidance of neurons on gold surfaces by directed assembly of proteins by atomic force microscopy. Biomaterials 30: 3397-3404.
- Hu, X.G., C. Viesselmann, S. Nam, E. Merriam and E.W. Dent. 2008. Activity-dependent dynamic microtubule invasion of dendritic spines. J. Neurosci. 28: 13094-13105.
- Kwiatkowski, A.V., D.A. Rubinson, E.W. Dent, J.E. van Veen, J.D. Leslie, J. Zhang, A.A. Burds, R.T. Bronson, S. Mori, R. Fässler, and F.B. Gertler. 2007. Ena/VASP is required for neuritogenesis in the developing cortex. Neuron 56: 441-55.
- Dent, E.W., A.V. Kwiatkowski, L. Mebane, U. Philippar, M. Barzik, D.A. Rubinson, C. Furman, A. Alberts, A.A. Burds, and F.B. Gertler. 2007. Filopodia are required for cortical neurite initiation. Nature Cell Biology, 9: 1347-59.
- Kalil, K. and E.W. Dent. 2005. Touch and go: guidance cues signal to the growth cone cytoskeleton. Current Opinions in Neurobiol. 15: 521-26.
- Kalil, K. and E.W. Dent. 2004. Hot +TIPS: Guidance cues signal directly to microtubules. Neuron 42: 877-79.
- Lebrand, C., E.W. Dent, G.A. Strasser, L.M. Lanier, M. Krause T. Svitkina, G.G. Borisy and F.B. Gertler. 2004. Critical Role of Ena/VASP proteins for filopodia formation in neurons and in function downstream of Netrin-1. Neuron 42: 37-49.
- Dent, E.W., A. Barnes, F. Tang and K. Kalil. 2004. Netrin-1 and Sema 3A promote or inhibit cortical axon branching respectively by reorganization of the cytoskeleton. J. Neurosci. 24:3002-12.
- Dent, E.W. and F.B. Gertler. 2003. Cytoskeletal dynamics and transport in growth cone motility and axon guidance. Neuron 40: 209-27.
- Krause, M., E.W. Dent, J.E. Bear, J.J. Loureiro and F.B. Gertler. 2003. Ena/VASP proteins: regulators of the actin cytoskeleton and cell migration. Ann. Rev. Cell and Dev. Biol. 19: 541-64.