Research Description
Regulation of Axon Guidance and Cytoskeletal Dynamics by Intracellular Signaling
Work in my laboratory focuses on the intracellular mechanisms that regulate growth cone motility and behavior. Growth cones are sensory-motor specializations at the tips of all growing axons and dendrites that detect and transduce extracellular cues into guided outgrowth. Great advances have been made in recent years in our understanding of the factors that contribute to guided axon extension. Many new classes of ligands and their receptors have been discovered and we are beginning to appreciate how growth cones integrate multiple extracellular stimuli and convert those signals into stereotyped behaviors.
Research in my laboratory combines a variety of fluorescent probe technologies with confocal microscopy to visualize the dynamic behavior of growth cones and assess their physiological responses during axon extension in vitro and guided outgrowth in the intact spinal cord. We use the African Clawed frog Xenopus Laevis as our model system due to the large size, rapid development, and ease of molecular and surgical manipulation of its embryos. Molecular expression as well as photolytic uncaging techniques are used to alter the physiology of growth cones both in vitro and in vivo. By combining the latest advances in imaging technologies with improved optical probes including fluorescent fusion proteins and FRET-based reporter molecules we hope to answer the following questions:
1. How does tyrosine kinase signaling by Src and FAK non-receptor tyrosine kinases regulate filopodial protrusion and growth cone motility downstream of axon guidance cues?
2. How do the Rho family of small GTPases regulate growth cone point contact formation and dynamics.
3. How does calcium influx and release through specific channels exert differential affects on neurite outgrowth.
4. What types of Trp channels are expressed by spinal cord neurons and what roles do they play in axon guidance and regeneration.
Recent Publications
Robles, E., Huttenlocher, A, Gomez, T. M. (2003). Filopodial calcium transients regulate growth cone motility and guidance through local activation of calpain. Neuron, 38, 597-609.
Gomez, T.M. (2005). Neurobiology: channels for pathfinding. Nature. 434, 835-838.
Robles, E., Woo, S and Gomez, T. M. (2005). Coincident Src and Cdc42 signals at the tips of growth cone filopodia regulate protrusion. J Neurosci. 25, 7615-7622.
Moon, M-s and Gomez, T. M. (2005). Adjacent pioneer commissural interneuron growth cones switch from contact avoidance to axon fasciculation after midline crossing. Devlp. Biol. 288, 474-486.
Kholmanskikh, S. S., Koeller, H. B., Wynshaw-Boris, A., Gomez, T. M., Letourneau, P. C. and Ross, E.M. (2006). Calcium-dependent interaction of Lis1 with IQGAP1 and Cdc42 promotes neuronal motility. Nature Neurosci., 9, 50-57.
Gomez, T. M. and Zheng, J. (2006). The molecular basis for Calcium-dependent axon pathfinding. Nature Reviews Neuroscience, 7, 115-125.
Woo, S. W. and Gomez, T. M. (2006). Rac1 and RhoA promote neurite outgrowth through formation and stabilization of growth cone point contacts. J Neurosci. 26(5), 1418-1428.
Jacques-Fricke, B.T., Seow, Y., Gottlieb, P. A., Sachs, F. and Gomez, T. M. (2006). Opposing regulation of neurite growth by Ca2+ influx through a mechanosensitive channel and release from intracellular stores. J Neurosci. 26(21), 5656-5664.
Robles, E. and Gomez, T. M. (2006). Focal adhesion kinase signaling at sites of integrin mediated adhesion controls axon pathfinding. Nat Neurosci. 9, 1274-1283.
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