- Professor, Department of Neuroscience
- (608) 262-8902
Ph.D. Massachusetts Institute of Technology
Growth and Guidance of Axons in the Mammalian Central Nervous System
Growing axons are tipped by motile growth cones that interact with guidance cues to find appropriate targets. In some CNS pathways axon branches rather than the primary growth cone extend into and innervate targets. We are using cultured neurons from the developing cortex and time lapse fluorescence digital imaging to determine mechanisms of axon branching. We are investigating how the cytoskeleton reorganizes during axon branching by fluorescently labeling actin filaments and microtubules with microinjection techniques and visualizing dynamic cytoskeletal movements in living cortical neurons. To determine how guidance cues influence the direction of axon growth, we are applying such molecules to cortical growth cones and visualizing their effects on the cytoskeleton. We are also imaging calcium oscillations to test their role in cortical axon branching and exploring the role of actin regulatory proteins in modulating rates of growth cone advance leading to development of axon branches.
- Kalil K, Dent EW. Branch management: mechanisms of axon branching in the developing vertebrate CNS. Nat Rev Neurosci. 2014 Jan;15(1):7-18. doi: 10.1038/nrn3650. Review.
Li L, Fothergill T, Hutchins BI, Dent EW, Kalil K. Wnt5a evokes cortical axon outgrowth and repulsive guidance by tau mediated reorganization of dynamic microtubules. Dev Neurobiol. 2013 Jul 2. doi: 10.1002/dneu.22102. [Epub ahead of print]
Hutchins BI, Li L, Kalil K.Wnt/calcium signaling mediates axon growth and guidance in the developing corpus callosum. Dev Neurobiol. 2011 Apr;71(4):269-83. doi: 10.1002/dneu.20846.
- Li, L., Hutchins, B.I. and Kalil, K., (2009) Wnt5a induces simultaneous cortical axon outgrowth and repulsive axon guidance through distinct signaling mechanisms. J Neurosci. 29: 5873-83. PMCID2697037
- Hutchins, B.I. and Kalil, K., (2008) Differential outgrowth of axons and their branches is regulated by localized calcium transients. J Neurosci. 28: 143-53. PMCID2474798
- Tang, F. and Kalil, K., (2005) Netrin-1 induces axon branching in developing cortical neurons by frequency-dependent calcium signaling pathways. J Neurosci. 25: 6702-15
- Kalil, K. and Dent, E.W., (2004) Hot +tips: Guidance cues signal directly to microtubules. Neuron. 42: 877-9
- Dent, E.W., Barnes, A.M., Tang, F. and Kalil, K., (2004) Netrin-1 and semaphorin 3a promote or inhibit cortical axon branching, respectively, by reorganization of the cytoskeleton. J Neurosci. 24: 3002-12