|Gerald B. Downes
Associate Professor of Biology
Ph.D.: Washington University, St.Louis
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 zebrafish embryo as our model system. The zebrafish embryo has several characteristics that make it particularly well-suited to study spinal cord networks. The embryos 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.
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 currently determining 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 glycinergic neurotransmission within the zebrafish spinal cord. Glycinergic neurotransmission is essential for 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 ß 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. The G protein subunit gene families. 1999. 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 ? subunits. Genomics 57: 173-6.
Downes, G.B. , Copeland, N., Jenkins, N.A., and Gautam, N. 1998. Structure And mapping of the G protein ?3 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 ß? complex. Cell Signal . 10: 447-55.