Research Interests
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.
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Representative Publications
Downes, G.B. and Granato, M. 2005. Supraspinal input is dispensable to generate
glycine-mediated locomotive behaviors in the zebrafish embryo. J. Neurobiology. In press.
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 β 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 γ subunits. Genomics 57: 173-6.
Downes, G.B., Copeland, N., Jenkins, N.A., and Gautam, N. 1998. Structure And
mapping of the G protein γ3 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 βγ
complex. Cell Signal. 10: 447-55.
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