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| Chi-Hon Lee, M.D., Ph.D., Investigator |
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Dr. Lee received his M.D. degree from China Medical College, Taiwan and his Ph.D. degree in Biophysics from the Rockefeller University, where he studied signal transduction by tyrosine kinases. During his postdoctoral training as a Life Sciences Research Foundation fellow at UCLA, he developed a genetic technique to study neuronal connectivity at single cell resolution. In 2002, he joined NICHD as an Investigator in the laboratory of Gene Regulation and Development. His group combines behavioral, imaging, and molecular genetic approaches to study visual circuit development and function in Drosophilia. He received NIH director's award 2008.
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Staff:
- Shuying Gao, Postdoctoral Fellow, (301) 469-3399 gaoshuyi@mail.nih.gov
- Songling Huang, Postdoctoral Fellow, (301) 496-3399 huangson@mail.nih.gov
- Moyi Li, Technician, (301) 496-3399 limoy@mail.nih.gov
- Chun-Yuan Ting, Postdoctoral Fellow, (301) 496-3399 tingch@mail.nih.gov
- Meiluen Yang, Postdoctoral Fellow, (301) 496-3399 yangmeil@mail.nih.gov
Research Interests:
We interested in two key questions in neurobiology: how do genetic programs direct the formation of precise neuronal connections during development and how do the resulting neural circuits guide animal behaviors. We use the Drosophila visual system as a model because this relatively simple system shares many characteristics with vertebrate brains. For visual system development, we have been focusing on the molecular mechanisms that regulate the formation of layer- and column-specific connections made by photoreceptor axons. Our previous studies show that the adhesion molecule N-cadherin and the receptor tyrosine phosphatase LAR are required for the targeting of R7 axons to appropriate brain layers. We recently uncovered that Activin/TGF-beta signaling is required for the formation of precise retinotopic maps. Disrupting components of Activin signaling pathway results in R7 axons invading neighboring columns without affecting layer-specific targeting (figure 1). The restriction of R7 growth cones to single columns is further reinforced by repulsive interactions mediated by protocadherin Flamingo.
For neural circuit function, we focus on the neuronal mechanism of color vision. We recently identified the first-order interneurons that receive direct synaptic inputs from photoreceptor neurons. These include three types of projection neurons, which likely function as color-opponent neurons, as well as one type of amacrine neurons. Using a series of genetic methods, we inactivated or restored the function of specific neuron subtypes and determined the behavioral consequences. We found that the amacrine neurons that pool multiple R7 inputs to projection neurons are required for animal's phototactic responses to ultraviolete light in preference to green light. By correlating the connectivity and functions of the first-order interneurons, we are now generating anatomical and functional maps for the visual circuits.
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Selected Recent Publications:
Ting, C.-Y., Herman, T., Yonekura S., Gao, S., Wang, J., Serpe, M., O'Connor, M.B., Zipursky, S.L., Lee, C.-H. (2007) Tiling of R7 axons in the Drosophila visual system is mediated both by transduction of an Activin signal to the nucleus and by mutual repulsion., Neuron 56, 793-806.
Rister, J., Pauls, D., Schnell, B., Ting, C.-Y., Lee, C.-H., Sinakevitch, I., Morante, J., Strausfeld, N.J., Ito, K., Heisenberg, M. (2007) Dissection of the Peripheral Motion Channel in the Visual System of Drosophila melanogaster., Neuron 56, 155-70.
Yonekura S., Lei Xu, Ting C.-Y., Lee C.-H. (2007) Adhesive but not signaling activity of Drosophila N-cadherin is essential for photoreceptor target selection., Dev. Biol. 304, 759-70.
Ting C.-Y., Lee C.-H. (2007) Visual circuit development. , Curr Opin Neurobiol. 17, 65-72.
Yonekura S., Ting C.-Y., Neves G., Hung K., Hsu S., Chiba A., Chess A., Lee C.-H. (2006) The variable transmembrane domain of Drosophila N-cadherin regulates adhesive activity. , Mol Cell Biol. 20, 6598-6608.
Ting C.-Y., Yonekura S., Chung, P., Hsu, S., Robertson, H.M., Chiba, A., Lee, C.-H. (2005) The protocadherin Flamingo is required for axon target selection in the Drosophila visual system., Nat Neurosci. 6, 557-63.
Ting C.-Y., Yonekura S., Chung, P., Hsu, S., Robertson, H.M., Chiba, A., Lee, C.-H. (2005) Drosophila N-cadherin functions in the first stage of the two-stage layer-selection process of R7 photoreceptor afferents., Development 132, 953-963.
All Selected Publications
Contact Information:
Dr. Chi-Hon Lee
Laboratory of Gene Regulating and Development
NICHD
Building 18T, Room #106
18 Library Drive, MSC 5431
Bethesda, MD 20892-5431
Telephone: (301) 435-1940 (office),
(301) 496-4491 (fax)
Email: leechih@mail.nih.gov
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