Erik W. Dent

 

 

Role of the Cytoskeleton in Axon Outgrowth and Guidance

E-mail: ewdent@wisc.edu

Research Strength: Development: Plasticity and Repair

The long-term goal of the lab will be to understand how the cytoskeleton and cytoskeletal-associated-proteins interact in response to guidance cues to sculpt the developing nervous system. Specifically, we are interested in understanding how the actin and microtubule cytoskeletons interact during nervous system development. We will study proteins that coordinate interactions between microtubules and actin filaments using genetic, molecular, biochemical and especially high resolution biophotonic approaches. Our working hypothesis is these microtubule-actin linking proteins serve crucial roles in neuritogenesis, axon guidance and are essential for the response of neurons to chemoattractants and chemorepellents. These actin/microtubule interactions may even play important roles in synapse formation and function. The initial goals of the lab will: 1) determine how selected MAPs function downstream of axon guidance cues, 2) probe for known and novel proteins that specifically associate with populations of postranslationally modified microtubules, 3) Investigate cytoskeletal dynamics underlying axon development in the cortex. We are also developing a microfluidics-based system to ask novel questions about how cortical neurons respond to changing gradients of guidance cues.

Selected Publications:

• 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. 2006. Filopodia and dynamic microtubules are essential for neurite formation in cortical neurons. Submitted.
• 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. 2006. Ena/VASP is required for cortical organization, neuritogenesis and fiber tract formation during cortical development. Submitted.
• 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.