Katherine Kalil

Growing axons are tipped by motile growth cones that interact with guidance cues to find appropriatetargets. 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.

Figure 1 (right) shows a developing cortical neuron with fluorescently labeled microtubules and actin filaments.

Selected Publications

• 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
• Kalil, K. and Dent, E.W., (2005) Touch and go: Guidance cues signal to the growth cone cytoskeleton. Current opinion in Neurobiology. 15: 521-6
• 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
• Tang, F., Dent, E.W. and Kalil, K., (2003) Spontaneous calcium transients in developing cortical neurons regulate axon outgrowth. J Neurosci. 23: 927-36
• Dent, E.W., Tang, F. and Kalil, K., (2003) Axon guidance by growth cones and branches: Common cytoskeletal and signaling mechanisms. The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry. 9: 343-53
• Dent, E.W. and Kalil, K., (2003) Dynamic imaging of neuronal cytoskeleton. Methods in Enzymology. 361: 390-407
• E. W. Dent and K. Kalil (2001) Axon Branching Requires Interactions between Dynamic Microtubules and Actin Filaments. Journal of Neuroscience 21(24): 9757-9769
• Szebenyi, G., E.W. Dent, J.L. Callaway, C. Seys, H. Lueth, and K. Kalil. (2001). FGF-2 promotes axon branching of cortical neurons by influencing morphology and behavior of the primary growth cone. J. Neurosci. 21: 3932-3941
• Kalil, K., G. Szebenyi, and E.W. Dent. (2000). Common mechanisms underlying growth cone guidance and axon branching (review). J. Neurobiol. 44: 145-158
• Nagashima, M., X.Z. Shi, E.W. Dent and K. Kalil. (1999). Cortical neurite outgrowth and growth cone behaviors reveal developmentally regulated cues in spinal cord membranes. J. Neurobiol. 39: 393-406.
• E.W. Dent, P.W. Baas and K. Kalil. (1999). Reorganization and movement of microtubules in axonal growth cones and developing interstitial branches. J. Neurosci. 19: 8894-8908
• Szebenyi, G., J. Callaway, E.W. Dent and K. Kalil. (1998). Interstitial branches develop from active regions of the axon demarcated by the primary growth cone during pausing behaviors. J. Neurosci. 18: 7930-7940.