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| Dr. Thomas Kidd |
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Trinity
College, Dublin, Ireland, B.A.mod., Genetics, 1990. The wiring of nervous systems is composed of axons, specialized extensions of neurons that transmit electrical impulses. Axons are frequently many times longer than the diameter of the neuron’s cell body. Therefore during development, axons must navigate long distances to their correct targets. We use the fruit fly, Drosophila melanogaster, as a model organism to study axon guidance. The genetics of Drosophila are extremely well developed and when combined with histochemical reagents, allow the behavior of single axons to be analyzed in vivo. Axon navigation relies on extracellular cues that attract and repel axons by modifying the behavior of the axonal cytoskeleton through the action of cell surface receptors. Other molecules in the extracellular matrix provide paths of least resistance through adhesive interactions. A major challenge in axon guidance is to identify more of these extracellular molecules that regulate axon guidance. Identifying novel extracellular cues and their receptors is a major focus of the laboratory. Uncovering novel and specialized instances of axon guidance may help decipher how signals at the cell surface modulate the cytoskeleton. Translation of research to vertebrate systems through collaboration with other UNR laboratories is an important component of the research. Human CNS axons fail to regenerate when injured, and one of the reasons may be that the spinal cord contains molecules that are inhibitory to the regenerating axon. For this reason, repulsive cues are of particular interest. On the other hand, attractive cues may stimulate not just axons to grow, but also neurons damaged by stroke and other conditions. Finally, an emerging theme in vascular biology is that many axon guidance molecules are reused in developing blood vessels and in tumor angiogenesis, making them of broader scientific interest. Selected Publications Kidd, T., Russell, C., Goodman, C.S. and Tear, G. (1998). Dosage sensitive and complimentary functions of roundabout and commissureless control axon crossing of the CNS midline. Neuron. 20:25-33. Kidd, T., Bland, K.S. and Goodman, C.S. (1999). Slit is the midline repellent for the Robo receptor in Drosophila. Cell. 96:785-794. Brose, K., Bland, K.S., Wang, K.H., Arnott, D., Henzel, W., Goodman, C.S., Tessier-Lavigne, M. and Kidd, T. (1999). Slit proteins bind Robo receptors and have an evolutionarily conserved role in repulsive axon guidance. Cell. 96:795-806. Wang, K.H., Brose, K., Arnott, D., Kidd, T., Goodman, C.S., Henzel, W. and Tessier-Lavigne, M. (1999). Biochemical purification of a mammalian slit protein as a positive regulator of sensory axon elongation and branching. Cell. 96:771-784. Bashaw, G.J., Kidd, T., Murray, D., Pawson, T. and Goodman, C.S. (2000). Repulsive axon guidance: Abelson and Enabled play opposing roles downstream of the roundabout receptor. Cell. 101:703-715. Simpson, J.H., Kidd, T., Bland, K.S. and Goodman, C.S. (2000). Short and long range guidance by slit and its Robo receptors. Robo and Robo2 play distinct roles in midline guidance. Neuron. 28:753-766. Kramer, S.G., Kidd, T., Simpson, J.H. and Goodman, C.S. (2001).
Switching repulsion to attraction: changing responses to slit during
transition in mesoderm migration. Science. 292:737-740.
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Contact Information: University of Nevada, Reno Office phone Additional Links: General review of axon guidance at the midlineInteractive Fly: The Interactive Fly - A cyberspace guide to Drosophila development and metazoan evolution Flybase Society for Neuroscience Brain Briefings Biotech links: www.exelixis.com www.renovis.com http://www.rinatneuro.com/ http://www.envivopharma.com/ |