Chi-Bin Chien
CHI-BIN CHIEN
e-mail: chi-bin.chien@neuro.utah.edu
The Chien Lab
Developmental Neuroscience
Molecular Neuroscience
Cellular Neuroscience B.A. 1981, Johns Hopkins University; Ph.D. 1991, California Institute of Technology; Postdoctoral Fellow, 1991-95, University of California San Diego; Postdoctoral Fellow, 1996-97, Max Planck Institute for Developmental Biology, Tuebingen, Germany
Confocal projection through a day 5 wholemounted zebrafish embryo, double-labelled with diI (red) and diO (green) in both eyes.
RESEARCH:
Axonal pathfinding in zebrafish mutants
Imagine trying to find your way from the University to downtown Salt Lake on foot, using only short-range senses (smell, touch, and taste, eyes closed). This gives an idea of the task faced by a growing axon in the developing brain. The growing tip of the axon, the growth cone, has to navigate a long way across complex terrain in order to connect up with its target neurons. Nevertheless, axons somehow find their way with incredible precision, allowing the developing embryo to build itself a functioning nervous system.
My lab studies the genes and cell behaviors that underlie axon guidance. We use the developing zebrafish visual system as a model, for several reasons. The larvae develop quickly, so experiments are quick. They are transparent, so we can watch cells behaving in the living animal. Molecular and embryological perturbations are easy, so that we can test the mechanisms that control retinal axons. Finally, retinal axon guidance is specifically affected in 27 known mutants, so we can study the genes involved.
We use two main approaches: starting with mutants and starting with molecules. For mutants, the first step is to find out what gene is affected. We have cloned three mutants: astray, an axon guidance receptor; boxer, a gene required for heparan sulfate proteoglycan metabolism; and nevermind, a protein that likely acts in controlling the cytoskeleton. All three of these genes are related to genes implicated in human disease. The next step is to understand how these genes work. We have used in vivo and in vitro experiments to discover some surprising things about how Astray and its ligands work. Now that we have cloned boxer and nevermind, we are starting similar detailed analyses. For molecules, we are mining the zebrafish genome for genes that may be important retinotectal pathfinding. We first check whether they are expressed at the appropriate time and place in the visual system, and then quickly test their functions using antisense morpholino knockdown.
For all of our experiments, we watch what the axons do in vivo. We use timelapse microscopy to watch living growth cones as they navigate in vivo, and have made transgenic lines that express green fluorescent protein (GFP) specifically in retinal axons.
Recently we have expanded our interests beyond axon guidance, in three directions. First, we are studying how the optic cup forms and is patterned early during development, using a combination of 4D timelapse imaging and genetic manipulations. These studies are complemented by a forward genetic screen looking for new genes involved in eye development. Second, we are starting a large-scale Gal4 enhancer trap screen to generate genetic reagents that we can use to label and manipulate neuronal cohorts that may be involved in higher-order visual processing. Third, we have an ongoing collaboration with Dean Li's lab to study how guidance ligands and receptors act in formation of the vasculature.
Selected Publications:
Pittman, A.J., Gaynes, J.A., and Chien, C.-B. nev (cyfip2) is required for retinal lamination and axon guidance in the zebrafish retinotectal system. Developmental Biology, 15:784-94. NIHMSID 212814. PMCID: PMC2914190.
Wan*, Y., Otsuna*, H., Chien, C.-B., and Hansen, C. (2009) An interactive visualization tool for multi-channel confocal microscopy data in neurobiology research. IEEE Trans. Vis. Comput. Graph., 15:1489-1496. *equal contributions.
Pittman, A.J.*, Law, M.Y.*, and Chien, C.-B. (2008) Pathfinding in a large vertebrate axon tract: isotypic interactions guide retinotectal axons at multiple choice points. Development, 135:2865-2871. *equal contributions
Hardy, M.E., Ross, L.V., and Chien, C.-B. (2007) Focal gene misexpression in zebrafish embryos induced by local heat shock using a modified soldering iron. Developmental Dynamics, 236:3071-3076.
Kwan, K.M., Fujimoto, E., Grabher, C., Mangum, B.D., Hardy, M.E., Campbell, D.S., Parant, J.M., Yost, H.J., Kanki, J.P., and Chien, C.-B. (2007) The Tol2kit: a multisite Gateway-based construction kit for Tol2 transposon transgenesis constructs. Developmental Dynamics, 236:3088-3099.
Campbell, D. S., Stringham, S.A., Timm, A., Xiao, T., Law, M. Y., Baier, H., Nonet, M. L., and Chien, C.-B. (2007) Slit1a inhibits retinal ganglion cell arborisation and synaptogenesis via Robo2-dependent and -independent pathways. Neuron, 55:241-235.
Suli, A., Mortimer, N., Shepherd, I., and Chien, C.-B. (2006) Netrin/DCC signaling controls contralateral dendrites of octavolateralis efferent neurons. Journal of Neuroscience, 26:13328-13337.
Wilson*, B. D., Ii*, M., Park*, K. W., Suli*, A., Sorensen, L. K., Larrieu-Lahargue, F., Urness, L. D., Suh, W., Asai, J., Kock, G. A. H., Thorne, T., Silver, M., Thomas, K. R., Chien, C.-B., Losordo, D. W., and Li, D. Y. (2006) Netrins promote developmental and therapeutic angiogenesis. Science, 313:640-644.*=equal contributions.
Lee, J. S., von der Hardt, S., Rusch, M. A., Stringer, S. E., Stickney, H. L., Talbot, W. S., Geisler, R., Nüsslein-Volhard, C., Selleck, S. B., Chien*, C.-B., and Roehl*, H. (2004) Axon sorting in the optic tract requires HSPG synthesis by ext2 (dackel) and extl3 (boxer). Neuron, 44:947-960. *=equal contributions.
Reviews:
Lee, J. S., and Chien, C.-B. (2004) When sugars guide axons: new insights from heparan sulphate proteoglycan mutants. Nature Reviews Genetics, 5:923-935.
Hutson, L. D., and Chien , C.-B. (2002) Axon guidance and synaptogenesis in zebrafish.Current Opinion in Neurobiology, 12:87-92.
Collaborative papers:
Jurrus, E., Hardy, M., Tasdizen, T., Fletcher, P.T., Koshevoy, P., Chien, C.-B., Denk, W., and Whitaker, R. (2008) Axon tracking in serial block-face scanning electron microscopy. Med Image Anal, 13:180-188.
Veien, E.S., Rosenthal, J.S., Kruse-Bend, R.C., Chien, C.-B., and Dorsky, R.I. (2008) Canonical Wnt signaling is required for maintenance of dorsal retinal identity. Development, 135:4101-4111.
Clément, A., Wiweger, M., von der Hardt, S., Rusch, M A., Selleck, S.B., Chien, C.-B., and Roehl, H.H. (2008) Regulation of zebrafish skeletogenesis by ext2/dackel and papst1/pinscher. PLoS Genet, 4: e1000136.
Navankasattusas, S.*, Whitehead, K.J.*, Suli, A., Sorensen, L.K., Lim, A.H., Zhao, J., Park, K.W., Wythe, J.E., Thomas, K.R., Chien, C.-B., and Li, D.Y. (2008) The netrin receptor, Unc5b, promotes angiogenesis in specific vascular beds. Development, 135:659-667. *equal contributions
e-mail: chi-bin.chien@neuro.utah.edu
Nov. 3, 1965 - Dec. 2, 2011
Professor of Neurobiology and AnatomyThe Chien Lab
Developmental Neuroscience
Molecular Neuroscience
Cellular Neuroscience B.A. 1981, Johns Hopkins University; Ph.D. 1991, California Institute of Technology; Postdoctoral Fellow, 1991-95, University of California San Diego; Postdoctoral Fellow, 1996-97, Max Planck Institute for Developmental Biology, Tuebingen, Germany
Confocal projection through a day 5 wholemounted zebrafish embryo, double-labelled with diI (red) and diO (green) in both eyes.
RESEARCH:
Axonal pathfinding in zebrafish mutants
Imagine trying to find your way from the University to downtown Salt Lake on foot, using only short-range senses (smell, touch, and taste, eyes closed). This gives an idea of the task faced by a growing axon in the developing brain. The growing tip of the axon, the growth cone, has to navigate a long way across complex terrain in order to connect up with its target neurons. Nevertheless, axons somehow find their way with incredible precision, allowing the developing embryo to build itself a functioning nervous system.
My lab studies the genes and cell behaviors that underlie axon guidance. We use the developing zebrafish visual system as a model, for several reasons. The larvae develop quickly, so experiments are quick. They are transparent, so we can watch cells behaving in the living animal. Molecular and embryological perturbations are easy, so that we can test the mechanisms that control retinal axons. Finally, retinal axon guidance is specifically affected in 27 known mutants, so we can study the genes involved.
We use two main approaches: starting with mutants and starting with molecules. For mutants, the first step is to find out what gene is affected. We have cloned three mutants: astray, an axon guidance receptor; boxer, a gene required for heparan sulfate proteoglycan metabolism; and nevermind, a protein that likely acts in controlling the cytoskeleton. All three of these genes are related to genes implicated in human disease. The next step is to understand how these genes work. We have used in vivo and in vitro experiments to discover some surprising things about how Astray and its ligands work. Now that we have cloned boxer and nevermind, we are starting similar detailed analyses. For molecules, we are mining the zebrafish genome for genes that may be important retinotectal pathfinding. We first check whether they are expressed at the appropriate time and place in the visual system, and then quickly test their functions using antisense morpholino knockdown.
For all of our experiments, we watch what the axons do in vivo. We use timelapse microscopy to watch living growth cones as they navigate in vivo, and have made transgenic lines that express green fluorescent protein (GFP) specifically in retinal axons.
Recently we have expanded our interests beyond axon guidance, in three directions. First, we are studying how the optic cup forms and is patterned early during development, using a combination of 4D timelapse imaging and genetic manipulations. These studies are complemented by a forward genetic screen looking for new genes involved in eye development. Second, we are starting a large-scale Gal4 enhancer trap screen to generate genetic reagents that we can use to label and manipulate neuronal cohorts that may be involved in higher-order visual processing. Third, we have an ongoing collaboration with Dean Li's lab to study how guidance ligands and receptors act in formation of the vasculature.
Selected Publications:
Pittman, A.J., Gaynes, J.A., and Chien, C.-B. nev (cyfip2) is required for retinal lamination and axon guidance in the zebrafish retinotectal system. Developmental Biology, 15:784-94. NIHMSID 212814. PMCID: PMC2914190.
Wan*, Y., Otsuna*, H., Chien, C.-B., and Hansen, C. (2009) An interactive visualization tool for multi-channel confocal microscopy data in neurobiology research. IEEE Trans. Vis. Comput. Graph., 15:1489-1496. *equal contributions.
Pittman, A.J.*, Law, M.Y.*, and Chien, C.-B. (2008) Pathfinding in a large vertebrate axon tract: isotypic interactions guide retinotectal axons at multiple choice points. Development, 135:2865-2871. *equal contributions
Hardy, M.E., Ross, L.V., and Chien, C.-B. (2007) Focal gene misexpression in zebrafish embryos induced by local heat shock using a modified soldering iron. Developmental Dynamics, 236:3071-3076.
Kwan, K.M., Fujimoto, E., Grabher, C., Mangum, B.D., Hardy, M.E., Campbell, D.S., Parant, J.M., Yost, H.J., Kanki, J.P., and Chien, C.-B. (2007) The Tol2kit: a multisite Gateway-based construction kit for Tol2 transposon transgenesis constructs. Developmental Dynamics, 236:3088-3099.
Campbell, D. S., Stringham, S.A., Timm, A., Xiao, T., Law, M. Y., Baier, H., Nonet, M. L., and Chien, C.-B. (2007) Slit1a inhibits retinal ganglion cell arborisation and synaptogenesis via Robo2-dependent and -independent pathways. Neuron, 55:241-235.
Suli, A., Mortimer, N., Shepherd, I., and Chien, C.-B. (2006) Netrin/DCC signaling controls contralateral dendrites of octavolateralis efferent neurons. Journal of Neuroscience, 26:13328-13337.
Wilson*, B. D., Ii*, M., Park*, K. W., Suli*, A., Sorensen, L. K., Larrieu-Lahargue, F., Urness, L. D., Suh, W., Asai, J., Kock, G. A. H., Thorne, T., Silver, M., Thomas, K. R., Chien, C.-B., Losordo, D. W., and Li, D. Y. (2006) Netrins promote developmental and therapeutic angiogenesis. Science, 313:640-644.*=equal contributions.
Lee, J. S., von der Hardt, S., Rusch, M. A., Stringer, S. E., Stickney, H. L., Talbot, W. S., Geisler, R., Nüsslein-Volhard, C., Selleck, S. B., Chien*, C.-B., and Roehl*, H. (2004) Axon sorting in the optic tract requires HSPG synthesis by ext2 (dackel) and extl3 (boxer). Neuron, 44:947-960. *=equal contributions.
Reviews:
Lee, J. S., and Chien, C.-B. (2004) When sugars guide axons: new insights from heparan sulphate proteoglycan mutants. Nature Reviews Genetics, 5:923-935.
Hutson, L. D., and Chien , C.-B. (2002) Axon guidance and synaptogenesis in zebrafish.Current Opinion in Neurobiology, 12:87-92.
Collaborative papers:
Jurrus, E., Hardy, M., Tasdizen, T., Fletcher, P.T., Koshevoy, P., Chien, C.-B., Denk, W., and Whitaker, R. (2008) Axon tracking in serial block-face scanning electron microscopy. Med Image Anal, 13:180-188.
Veien, E.S., Rosenthal, J.S., Kruse-Bend, R.C., Chien, C.-B., and Dorsky, R.I. (2008) Canonical Wnt signaling is required for maintenance of dorsal retinal identity. Development, 135:4101-4111.
Clément, A., Wiweger, M., von der Hardt, S., Rusch, M A., Selleck, S.B., Chien, C.-B., and Roehl, H.H. (2008) Regulation of zebrafish skeletogenesis by ext2/dackel and papst1/pinscher. PLoS Genet, 4: e1000136.
Navankasattusas, S.*, Whitehead, K.J.*, Suli, A., Sorensen, L.K., Lim, A.H., Zhao, J., Park, K.W., Wythe, J.E., Thomas, K.R., Chien, C.-B., and Li, D.Y. (2008) The netrin receptor, Unc5b, promotes angiogenesis in specific vascular beds. Development, 135:659-667. *equal contributions
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