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Neuroscience Graduate Program at UCSF
Development and Function of Monoamine Neural Systems
We are interested in two fundamental questions: 1) how do pluripotent progenitor cells develop into functional cell types? 2) How do functional cell types assemble into neural circuits that regulate behavior? We use monoaminergic cells as our model cell types and entry points.
In the vertebrate nervous system, there rests small groups of neurons that use neurotransmitters dopamine (DA), noradrenaline (NA), or serotonin (5HT) to convey information. The importance of these neurons is underscored by their involvement in many human neurological disorders including Parkinson's disease, sleep disorders, anxiety and depression, schizophrenia and addiction. The goal of our research is to define the causes and to help develop novel therapeutic interventions for these devastating human disorders, through understanding fundamental molecular and cellular mechanisms underlying the development and function of these neurotransmitter systems.
To understand how pluropotent progenitor cells become committed to specific neuronal types, we take a genetic approach in zebrafish. Through mutagenesis screening, we isolated zebrafish mutants that affect subsets of DA, NA, and 5HT neurons. Molecular cloning identified important transcription regulators in the process. Furthermore, as our previous screen is limited to one developmental stage and far from reaching saturation, we are carrying out additional screens. We also use cultured stem cells to address this question.
To study neuronal function, we are interested in simple and tractable behavioral /physiological responses and their modulation by drugs of abuse in particular alcohol. We are currently studying camouflage and light/dark choice behavior in zebrafish.
1. Screening and molecular genetic characterization of mutations affecting DA, NA, and 5HT neuron development.
2. Screening and molecular genetic characterization of mutations affecting camouflage and modulation by ethanol.
3. Determine brain DA and NA neuronal connective patterns through analysis of regulatory elements and GFP transgenesis.
4. Study a light/dark choice behavior in zebrafish.
Keerthi Krishnan
Graduate Student
Qiang Li
Postdoctoral Fellow
Michael Munchua
Lab Assistant
Hui Chen
Specialist
Jisong Peng
Postdoctoral Fellow
Thomas Mueller
Postdoctoral Fellow
Zhiqiang Dong
Postdoctoral Fellow
Nan Yang
Graduate student
Priya Mathur
Specialist
Lishan Chen
Postdoctoral Fellow
Mahendra Wagle
Postdoctoral Fellow
Michael Berberoglu
Graduate Student
Hadie Khodabakhsh
Staff Research Associate
Lee, S.A., Shen, E.L., Fiser, A., Sali, A., and Guo, S. (2003) The zebrafish forkhead transcription factor Foxi1 specifies epibranchial placode-derived sensory neurons. Development 130, 2669-2679.
Guo, S. (2004) Linking genes to brain, behavior, and neurological diseases: what can we learn from zebrafish? Genes, Brain and Behavior 3, 63-74.
Lockwood, B., Bjerke, S., Kobayashi, K., and Guo, S. (2004) Acute effects of alcohol on larval zebrafish: a genetic system for large-scale screening. Pharmacology Biochemistry and Behavior 77, 647-654.
Rink, E., and Guo, S. (2004) The too few mutant selectively affects subgroups of monoaminergic neurons in the zebrafish forebrain. Neuroscience 127, 147-154.
Bretaud, S., Lee, S., and Guo, S. (2004) Sensitivity of zebrafish to environmental toxins
implicated in Parkinson’s disease. Neurotoxicology and teratology, 26, 857-864 (2004)
Jeong, J., Einhorn, Z., Mercurio S, Lee S, Lau B, Mione M, Wilson SW, Guo, S. Neurogenin1 is a determinant of zebrafish basal forebrain dopaminergic neurons and is regulated by the conserved zinc finger protein Tof/Fezl. Proc. Natl. Acad. Sci. 103, 5143-5148 (2006).
B. Lau, S. Bretaud, Y. Huang, E.Lin, and S. Guo. Dissociation of food and opiate preference by a genetic mutation in zebrafish. Genes Brain and Behavior, 5 (7): 497-505 (2006).
Wang, X., Yang, N., Uno, E., Roeder, R.G., and Guo, S. A subunit of the mediator complex regulates vertebrate neuronal development. Proc. Natl. Acad. Sci. 103 (46): 17284-9 (2006).
Jeong, J., Einhorn, Z., Mathur, P., Chen, L., Lee, S., Kawakami, K., and Guo, S. Patterning the zebrafish diencephalon by the conserved zinc finger protein Fezl. Development 134, 127-136 (2007).
Bretaud, S., Li, Q., Lockwood, L.L., Kobayashi, K., Lin, E., and Guo, S. A choice behavior for morphine reveals experience-dependent drug preference and underlying neural substrates in developing larval zebrafish. Neuroscience 146, 1109-1116 (2007).
Su Guo, Ph.D.
Phone
415-502-4949
Physical Address
Rock Hall
Room 484D
Mission Bay 19B
Mailing Address
Room 484D
Genetics Developement and Behavioral Sciences Building
UCSF
1550 4th Street
San Francisco, CA 94143-2811
For Internal Campus Mail
Box 2811
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