Office: 427C Morrill II South
B.S., Johnson C. Smith University, 1992
Ph.D., Washington University, St. Louis, 1999
University of Pennsylvania, 1999-2005
Development and Function of Spinal Cord Networks
Groups of neurons within the spinal cord coordinate the precise movements of locomotive behavior, such as walking or swimming. Our laboratory is interested in the development, organization, and function of these neuronal networks and we use the developing zebrafish as our model system. Zebrafish embryos and larvae have several characteristics that make them particularly well-suited to study spinal cord networks: They demonstrate robust swimming behavior, their spinal cords are relatively simple compared to mammalian spinal cords, the embryos are transparent so spinal cord development can be easily observed, and a large array of genetic resources are available. These features allow us to take an integrated genetic, molecular, cellular, and behavioral approach to study the spinal cord networks that orchestrate locomotive behavior. Since spinal cord organization is broadly conserved among vertebrates, our work holds promise to provide insight into mammalian spinal cords and it provides new models of human disease.
One approach we are taking to examine spinal cord networks utilizes zebrafish mutants that demonstrate abnormal locomotive behavior, indicating that they contain spinal cord network defects. Instead of performing the normal left and right tail flips that comprise swimming behavior, one group of mutants exhibit nose to tail compressions, similar to the accordion musical instrument, and another group of mutants demonstrate uncoordinated, spastic behavior. We are analyzing the cellular and molecular defects in these mutants with the goal of identifying the potentially novel genes and neurons required for locomotive behavior. Complementing this approach, we are also examining the organization and function of GABAergic neurotransmission within the zebrafish spinal cord. GABA is a key neurotransmitter that controls normal locomotive behavior, and we are interested in elucidating the multiple roles it plays during the development of spinal cord networks.
de Soysa, Y.T., Ulrich, A., Friedrich, T., Pite, D., Compton, S., Ok, D., Bernardos, R.L., Hsieh, S., Downes, G.B., Rachael Stein, Lagdameo, M.C., Halvorsen, K., and Barresi, M.J.F. 2012. Macondo crude oil from the Deepwater Horizon oil spill disrupts specific developmental processes during zebrafish embryogenesis. BMC Biology, 10: 40.
Khan, T.M., Benaich, N., Malone, C.F., Bernandos, R.L., Russell, A.R., Downes, G.B., Barresi, M.J., and Hutson, L.D. 2012. Vincrisitne and bortezomib cause axon outgrowth and behavioral defects in larval zebrafish. Journal of the Peripheral Nervous System, 17: 76-89.
Friedrich, T., Lambert, A.M., Masino, M.A., and Downes, G.B. 2012. Mutation of zebrafish dihydrolipoyl transacylase results in abnormal motor behavior and models maple syrup urine disease. Disease Models and Mechanisms, 5: 248-58.
McKeown, K.A., Moreno, R., Hall, V.L., Ribera, A.B., and Downes, G.B. 2012. Zebrafish technotrouser mutants demonstrate abnormal locomotive behavior development due to mutation of a glutamate transporter. Developmental Biology, 362: 162-71.
Olson, B.D., Sgourdou, P., and Downes, G.B. 2010. Analysis of a zebrafish behavioral mutant reveals a dominant mutation in atp2a1/SERCA1. Genesis, 48: 354-61.
McKeown, K.A., Downes, G.B., and Hutson, L.D. 2009. Modular Laboratory Exercises to analyze the development of zebrafish motor behavior. Zebrafish, 6: 179-85.
Downes, G.B. and Granato, M. 2006. Supraspinal input is not required to generate glycine-mediated locomotive behaviors in the zebrafish embryo. J. Neurobiology, 66: 437-51.
Hiromi, H., Saint-Amant, L., Downes, G.B., Cui, W.W., Zhou, W., Granato, M., Kuwada, J.Y. 2005. Zebrafish bandoneon mutants display behavioral defects due to a mutation in the glycine receptor beta subunit. P.N.A.S., 102: 8345-50.
Downes, G.B. and Granato, M. 2004. Acetylcholinesterase function is dispensable for neurite growth but is critical for neuromuscular synapse stability. Developmental Biology, 270: 232-45.
Downes, G.B., Waterbury, J.A., and Granato, M. 2002. Rapid in vivo labeling of identified zebrafish neurons. Genesis, 34: 196-202.
Downes, G.B. and Gautam, N. 1999. The G protein subunit gene families. Genomics, 62: 447-55.
Downes, G.B., Gilbert, D.J., Copeland, N.G., Gautam, N. and Jenkins, N.A. 1999. Chromosomal mapping of five mouse G protein g subunits. Genomics, 57: 173-6.
Downes, G.B., Copeland, N., Jenkins, N.A., and Gautam, N. 1998. Structure And mapping of the G protein gamma3 subunit gene and a divergently transcribed novel gene, Gng3lg. Genomics, 15: 220-30.
Gautam, N., Downes, G.B., Yan, K., and Kisselev, O. 1998. The G protein beta-gamma complex. Cell Signal, 10: 447-55.
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