Faculty Profile

Fields of Study

Molecular Genetics of Nervous System Development and Function..

Areas of Focus

Development
Neurobiology & Animal Physiology

Research Interest

We are interested in identifying and understanding genes that regulate the formation and function of neural circuits in the vertebrate CNS.

About John Kuwada

The Kuwada lab is interested in genes that regulate the development and function of neural circuits and the behaviors they subserve. The lab studies zebrafish since they are transparent, accessible and manipulable at all stages of development, and are vertebrates in which genes can be manipulated by mutagenesis and by the generation of transgenic animals. We generate and analyze behavioral mutations in order to molecularly identify neural genes. The function of these genes are analyzed by electrophysiology, Ca2⁺ imaging, and imaging of fluorescently labeled proteins within neural circuits of living zebrafish in addition to other cellular and molecular genetic methods. Neural circuits are characterized by genetically manipulating them to see how these manipulations affect circuit function and behavior. Mutations being examined include ones that affect the localization of neurotransmitter receptors, signaling by sensory neurons and regulation of voltage-dependent channels. Many of the mutated genes identified in zebrafish have counterparts in humans that cause neurological diseases. The lab is also applying the molecular genetic methods to examine the neural basis of aggressive behavior.

Dr. Kuwada received his Ph.D. from Stanford in 1980, was an NSF and NIH postdoctoral fellow at UCSD, and a research associate at Stanford. In 1994 he was a Visiting Professor at Basel University and in 1999 a Visiting Scientist at the RIKEN Institute in Tokyo, Japan.

Publications

Dowling, J.J., Vreede, A., Low, S.E., Kuwada, J.Y., Bonnemann, C. and Feldman, E.L. (2009). "Loss of myotubularin function results in T-tubule disorganization in zebrafish and human myotubular myopathy." PLoS Genetics 5:e1000372.

Bruneau, E.G., Brenner D.S., Kuwada, J.Y. and Akaaboune, M. (2008). "Acetylcholine receptor clustering is required for the accumulation and maintenance of post-synaptic scaffolding proteins." Current Biology 18: 109-115. Read Publication.

Low, S.E., Kuwada, J.Y. and Hume, R.I. (2008). "Amino acid variations resulting in functional and nonfunctional zebrafish P2X1 and P2X5.1 receptors." Purinergic Signaling 4:383-92.

Zhou W, Horstick EJ, Hirata H, and Kuwada J.Y. (2008). "Identification and expression of voltage-gated calcium channel beta subunits in Zebrafish." Dev Dyn 237:3842-52.

Saint-Amant, L., Sprague, S.M., Hirata, H., Li, Q., Cui, W.W., Zhou, W., Poudou, O., Hume, R.I. and Kuwada, J.Y. (2008). "The zebrafish ennui behavioral mutation disrupts acetylcholine receptor localization and motor stability." Developmental Neurobiology 68: 45-61.

Hirata, H., Watanabe, T., Hatakeyama, J., Sprague, S.M., Saint-Amant, L., Nagashima, A., Cui, W.W., Zhou, W., and Kuwada, J.Y. (2007). "Zebrafish relatively-relaxed mutants have a ryanodine receptor defect, exhibit slow swimming and provide a model of multi-minicore disease." Development 134: 2771-2781.

Zhou, W., Saint-Amant, S., Hirata, H., Cui, W.W., Sprague, S.M. and Kuwada, J.Y (2006). "Non-sense mutations in the dihydropyridine receptor β1 gene, CACNB1, paralyze zebrafish relaxed mutants." Cell Calcium 39: 227-236. Read Publication.

Zhou, W., Shirabe, K., Thisse, C., Thisse, B., and Kuwada, J.Y (2006). "Molecular cloning and expression of two small leucine-rich proteoglycan (SLRP) genes, dspg3l and optcl, in zebrafish." Gene Exp. Patterns 6: 482-488. Read Publication.

Sato-Maeda, M., Tawarayama, H., Obinata, M., Kuwada, J.Y. and Shoji, W (2006). "Sema3A1 guides spinal motor axons in a cell and stage specific manner in zebrafish." Development 133: 937-947. Read Publication.

Cui, W.W., Low, S., Hirata, H. Geisler, R., Hume, R.I. and Kuwada, J.Y (2005). "The zebrafish sho gene encodes a glycine transporter and is essential for the function of early neural circuits in the CNS." J. Neurosci. 25: 6610-6620. Read Publication.

Hirata, H., Saint-Amant, L., Downes, G.B., Cui, W.W., Zhou, W., Granato, M., and Kuwada, J.Y (2005). "Zebrafish bandoneon mutants display behavioral defects due to a mutation in the glycine receptor β subunit." Proc. Natl. Acad. Sci. USA 102: 8345-8350. Read Publication.

Li, Q., Shirabe, K., Thisse, C., Thisse, B., Okamoto, H., Masai, I., and Kuwada, J.Y (2005). "Chemokine signaling guides axons within the retina in zebrafish." J Neurosci. 25: 1711-1717.

Haenisch, C., Diekmann, H., Klinger, M., Gennarini, G., Kuwada, J.Y. and Stuermer, C.A.O (2005). "The neuronal growth and regeneration associated Cntn1 (F3/F11/Contactin) gene is duplicated in fish: expression during development and retinal axon regeneration." Molecular and Cellular Neurosci. 28: 361-374.

Hirata, H., Saint-Amant, L., Waterbury, J., Cui, W., Zhou, W., Li, Q., Goldman, D.J., Granato, M. and Kuwada, J.Y (2004). "Accordion, a zebrafish behavioral mutant, has a muscle relaxation defect due to a mutation in the ATPase calcium pump SERCA1." Development 131: 5457-5468.

Song, M.H., Brown, N.L. and Kuwada, J.Y (2004). "The curly fry mutation deregulates cell divisions in a stage-dependent manner in zebrafish embryos." Dev. Biol. 276: 194-206.

Cui, W., Saint-Amant, L. and Kuwada, J.Y (2004). "The shocked Gene is Required for the Function of a Premotor Network in the Zebrafish CNS." J. Neurophysiol 92: 2898-2908.

Yeo, S-Y., Miyashita, T., Fricke, C., Little, M.H., Yamada, T., Kuwada, J.Y., Huh, T-L., Chien, C-B., and Okamoto, H (2004). "Involvement of Islet-2 in the Slit signaling for axonal branching and defasciculation of the sensory neurons in embryonic zebrafish ." Mech. Dev. 121: 315-324.

Li, Q., Shirabe, K. and Kuwada, J.Y (2004). "Chemokine signaling regulates sensory cell migration in zebrafish." Dev. Biol. 269: 123-136.

Liu, Y., Berndt, B., Su, F., Tawarayama, H., Shoji, W., Kuwada, J.Y. and Halloran, M.C (2004). "Semaphorin3D guides retinal axons along the dorsalventral axis of the tectum." J. Neurosci. 24: 310-318.

Shoji, W., Isogai, S., Sato-Maeda, M., Obinata, M. and Kuwada, J.Y (2003). "Semaphorin 3A1 regulates angioblast migration and vascular development in zebrafish embryos." Development 130: 3227-3236.

Xiao, T., Shoji, W., Zhou, W., Su, F., and Kuwada, J.Y (2003). "Transmembrane Sema4E guides branchiomotor axons to their targets in zebrafish." J. Neurosci. 23: 4190-4198.

Geling, A., Itoh, M., Tallafuss, A., Chapouton, P., Tannhauser, B., Kuwada, J.Y., Chitnis, A.B., and Bally-Cuif, L (2003). "bHLH transcription factor Her5 links patterning to regional inhibition of neurogenesis at the midbrain-hindbrain boundary." Development 130: 1591-1604.

Matsumoto, J., Zhou, W., Chen, F.F., Su, F., Kuwada, J.Y., Hidaka, E., Katsuyama, T., Sagara, J., Taniguchi, S., Ngo-Hazelett, P., Postlethwait, J.H., Nunez, G. and Inohara, N (2003). "Caspy: a zebrafish pyrin domain-containing caspase acitvated by asc oligomerization." J Biol. Chem. 278: 4268-4276.