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Research
General Information
ZIRC
ZFIN ID: ZDB-LAB-981125-13
Chien Lab
PI/Director: Chien, Chi-Bin
Contact Person: Chien, Chi-Bin
Email: chi-bin.chien@neuro.utah.edu
URL: http://chien.neuro.utah.edu/
Address: Department of Neurobiology and Anatomy University of Utah Medical Center 409 Wintrobe 20 North 1900 East Salt Lake City, UT 84132 USA
Country: United States
Phone: (801) 585-1702
Fax: (801) 581-4233
Line Designation: zc


GENOMIC FEATURES ORIGINATING FROM THIS LAB
Show first 50 of 122 genomic features


STATEMENT OF RESEARCH INTERESTS
The lab's overall interest is in how cell movements are controlled in the context of an intact, developing organism.

Axon guidance

Our largest effort focuses on how the growth cone guides the growing axon as it navigates through the brain, using the retinotectal system as a model. We use four different approaches, with the long-term aim of elucidating all of the genes and molecules that help to guide retinal axons to their targets, and understanding their functions in vivo.

1) Understanding the mutants. Several years ago we cloned the astray mutant and showed that it is defective in Robo2, a guidance receptor expressed in retinal ganglion cells (RGCs). We have characterized in detail the cell biological function of this receptor and its presumed ligands, the Slits. We have also cloned the boxer and dackel mutants (in collaboration with Henry Roehl), and found that they are defective in heparan sulfate proteoglycan (HSPG) synthesis. We are now working to define exactly how and when HSPGs act in optic tract sorting. Finally, we have cloned the nevermind mutant, defective in the cyfip2 gene, which encodes a protein in the WAVE complex that also binds to FMR1 family members.

2) Understanding the roles of candidate pathfinding molecules. Homologs of several molecules including Roundabout, neogenin, neuropilin, DCC, and unc5 are expressed in RGCs. We are developing techniques to transiently express wildtype and mutated forms of these molecules in RGCs, to test their role in retinal axon guidance.

3) Understanding how growth cones behave in vivo. We have developed techniques to make in vivo timelapse movies of navigating retinal growth cones, and are characterizing their dynamic behavior in both mutant and wildtype embryos. We have also developed several transgenic lines that express fluorescent protein markers in retinal axons.

4) Screening for new genes. We have carried out a large-scale noncomplementation screen for new robo2 alleles, and have an ongoing screen to look for mutants defective in early eye morphogenesis and patterning.

Cell motility in other contexts

Other projects in the lab study vascular guidance, dorsoventral eye patterning, and eye morphogenesis.

5) In the vascular system, we have been studying the role of the Netrin1a pathway in guiding secondary intersegmental sprouts to turn laterally and then anteroposteriorly at the horizontal myoseptum. These "parachordal" cells are of particular interest since they are the precursors of the zebrafish's lymphatic system.

6) We are studying the roles of the Bmp, Wnt, and Tbx pathways in controlling dorsoventral identity in the eye: initiation, maintenance, and refinement of dorsal identity, and eventually topographic axon guidance.

7) We have used 4D in toto imaging to visualize the development of the optic vesicle between 12-24 hpf, and have discovered several unappreciated cell movements, as well as defining fate maps of the eye's three main components: neural retina, retinal pigment epithelium, and lens.

Common resources

Finally, we are heavily involved in developing community resources:

8) To easily manipulate gene expression and generate transgenic lines, we developed the Tol2kit set of plasmids for multisite Gateway cloning of Tol2 expression constructs.

9) To visualize multichannel confocal datasets (both 3D and 4D), we have collaborated with Chuck Hansen's group in the University of Utah's Scientific Computing Institute to develop FluoRender, a freely-distributed volume rendering program, optimized to deliver useful visualizations quickly and with precision.

10) We are currently conducting a Gal4 enhancer trap screen, for which we are documenting expression patterns by widefield and confocal microscopy; lines will be distributed through ZIRC. We have discovered many beautiful patterns, including ones that label specific cells in the skin, lateral line, and nervous system. This work is funded by the NIMH under the rubric of the Zebrafish Tools initiative.


LAB MEMBERS
Otsuna, Hideo Post-Doc Bend, Renee Graduate Student Gaynes, John Graduate Student
Hörndli, Coni Stacher Graduate Student Law, Mei-Yee Graduate Student Lim, Amy Graduate Student
Rasband, Kendall Graduate Student Benko, Kevin Technical Staff Fujimoto, Esther Technical Staff
Gaynes, Brooke Technical Staff Quist, Tyler Technical Staff Rosenthal, Jude Technical Staff
Scoresby, Aaron Technical Staff


ZEBRAFISH PUBLICATIONS OF LAB MEMBERS x
Xie, Y., Kaufmann, D., Moulton, M.J., Panahi, S., Gaynes, J.A., Watters, H.N., Zhou, D., Xue, H.H., Fung, C.M., Levine, E.M., Letsou, A., Brennan, K.C., Dorsky, R.I. (2017) Lef1-dependent hypothalamic neurogenesis inhibits anxiety. PLoS Biology. 15:e2002257
Wan, Y., Otsuna, H., Holman, H.A., Bagley, B., Ito, M., Lewis, A.K., Colasanto, M., Kardon, G., Ito, K., Hansen, C. (2017) FluoRender: joint freehand segmentation and visualization for many-channel fluorescence data analysis. BMC Bioinformatics. 18:280
Eisenhoffer, G.T., Slattum, G., Ruiz, O.E., Otsuna, H., Bryan, C.D., Lopez, J., Wagner, D.S., Bonkowsky, J.L., Chien, C.B., Dorsky, R.I., Rosenblatt, J. (2017) A toolbox to study epidermal cell types in zebrafish. Journal of Cell Science. 130(1):269-277
Bryan, C.D., Chien, C.B., Kwan, K.M. (2016) Loss of laminin alpha 1 results in multiple structural defects and divergent effects on adhesion during vertebrate optic cup morphogenesis. Developmental Biology. 416(2):324-37
Gaynes, J.A., Otsuna, H., Campbell, D.S., Manfredi, J.P., Levine, E.M., Chien, C.B. (2015) The RNA Binding Protein Igf2bp1 Is Required for Zebrafish RGC Axon Outgrowth In Vivo. PLoS One. 10:e0134751
Otsuna, H., Hutcheson, D., Duncan, R., McPherson, A., Scoresby, A., Gaynes, B., Tong, Z., Fujimoto, E., Kwan, K., Chien, C., Dorsky, R. (2015) High-resolution analysis of CNS expression patterns in zebrafish Gal4 enhancer-trap lines. Developmental dynamics : an official publication of the American Association of Anatomists. 244(6):785-96
Hutcheson, D., Otsuna, H., Chien, C.B., Dorsky, R. (2014) Enhancer Trap Mutants Gal4 Project. ZFIN Direct Data Submission.
Hutcheson, D., Otsuna, H., Chien, C.B., Dorsky, R. (2014) Enhancer Trap Mutants Gal4 Project, Supplemental Data. ZFIN Direct Data Submission.
Xing, L., Quist, T.S., Stevenson, T.J., Dahlem, T.J., Bonkowsky, J.L. (2014) Rapid and efficient zebrafish genotyping using PCR with high-resolution melt analysis. Journal of visualized experiments : JoVE. (84):e51138
Deng, Y., Boon, C., Chen, S., Lim, A., and Zhang, L.H. (2013) Cis-2-dodecenoic acid signal modulates virulence of Pseudomonas aeruginosa through interference with quorum sensing systems and T3SS. BMC microbiology. 13(1):231
Gassman, A., Hao le, T., Bhoite, L., Bradford, C.L., Chien, C.B., Beattie, C.E, and Manfredi, J.P. (2013) Small molecule suppressors of Drosophila Kinesin deficiency rescue motor axon development in a zebrafish model of spinal muscular atrophy. PLoS One. 8(9):e74325
Hutcheson, D., Otsuna, H., Chien, C.B., Dorsky, R. (2013) Enhancer Trap Mutants, Gal4 Project. ZFIN Direct Data Submission.
Nguyen, T.K., Tran, V.M., Venkataswamy, S., Eriksson, I., Kojima, A., Koketsu, M., Loganathan, D., Kjellén, L., Dorsky, R.I., Chien, C.B., and Kuberan, B. (2013) Dimerized glycosaminoglycan chains increase FGF signaling during zebrafish development. ACS Chemical Biology. 8(5):939-48
Poulain, F.E., and Chien, C.B. (2013) Proteoglycan-mediated axon degeneration corrects pretarget topographic sorting errors. Neuron. 78(1):49-56
Kruse-Bend, R., Rosenthal, J., Quist, T.S., Veien, E.S., Fuhrmann, S., Dorsky, R.I., and Chien, C.B. (2012) Extraocular ectoderm triggers dorsal retinal fate during optic vesicle evagination in zebrafish. Developmental Biology. 371(1):57-65
Wang, X., Kopinke, D., Lin, J., McPherson, A.D., Duncan, R.N., Otsuna, H., Moro, E., Hoshijima, K., Grunwald, D.J., Argenton, F., Chien, C.B., Murtaugh, L.C., and Dorsky, R.I. (2012) Wnt signaling regulates postembryonic hypothalamic progenitor differentiation. Developmental Cell. 23(3):624-636
Hörndli C.S., and Chien, C.B. (2012) Sonic hedgehog is indirectly required for intraretinal axon pathfinding by regulating chemokine expression in the optic stalk. Development (Cambridge, England). 139(14):2604-2613
Bonner, J., Letko, M., Nikolaus, O.B., Krug, L., Cooper, A., Chadwick, B., Conklin, P., Lim, A., Chien, C.B., and Dorsky, R.I. (2012) Midline crossing is not required for subsequent pathfinding decisions in commissural neurons. Neural Development. 7(1):18
Eisenhoffer, G.T., Loftus, P.D., Yoshigi, M., Otsuna, H., Chien, C.B., Morcos, P.A., and Rosenblatt, J. (2012) Crowding induces live cell extrusion to maintain homeostatic cell numbers in epithelia. Nature. 484(7395):546-549
Lakhina, V., Marcaccio, C.L., Shao, X., Lush, M.E., Jain, R.A., Fujimoto, E., Bonkowsky, J.L., Granato, M., and Raper, J.A. (2012) Netrin/DCC Signaling Guides Olfactory Sensory Axons to Their Correct Location in the Olfactory Bulb. The Journal of neuroscience : the official journal of the Society for Neuroscience. 32(13):4440-4456
Kwan, K.M., Otsuna, H., Kidokoro, H., Carney, K.R., Saijoh, Y., and Chien, C.B. (2012) A complex choreography of cell movements shapes the vertebrate eye. Development (Cambridge, England). 139(2):359-372
Stevenson, T.J., Trinh, T., Kogelschatz, C., Fujimoto, E., Lush, M.E., Piotrowski, T., Brimley, C.J., and Bonkowsky, J.L. (2012) Hypoxia Disruption of Vertebrate CNS Pathfinding through EphrinB2 Is Rescued by Magnesium. PLoS Genetics. 8(4):e1002638
Xing, L., Hoshijima, K., Grunwald, D.J., Fujimoto, E., Quist, T.S., Sneddon, J., Chien, C.B., Stevenson, T.J., and Bonkowsky, J.L. (2012) Zebrafish foxP2 Zinc Finger Nuclease Mutant Has Normal Axon Pathfinding. PLoS One. 7(8):e43968
Fujimoto, E., Gaynes, B., Brimley, C.J., Chien, C.B., and Bonkowsky, J.L. (2011) Gal80 intersectional regulation of cell-type specific expression in vertebrates. Developmental dynamics : an official publication of the American Association of Anatomists. 240(10):2324-34
Lim, A.H., Suli, A., Yaniv, K., Weinstein, B., Li, D.Y., and Chien, C.B. (2011) Motoneurons are essential for vascular pathfinding. Development (Cambridge, England). 138(17):3847-3857
Fujimoto, E., Stevenson, T.J., Chien, C.B., and Bonkowsky, J.L. (2011) Identification of a Dopaminergic Enhancer Indicates Complexity in Vertebrate Dopamine Neuron Phenotype Specification. Developmental Biology. 352(2):393-404
Choi, J.H., Law, M.Y., Chien, C.B., Link, B.A., and Wong, R.O. (2010) In vivo development of dendritic orientation in wild-type and mislocalized retinal ganglion cells. Neural Development. 5:29
Wyatt, C., Ebert, A., Reimer, M.M., Rasband, K., Hardy, M., Chien, C.B., Becker, T., and Becker, C.G. (2010) Analysis of the astray/robo2 Zebrafish Mutant Reveals that Degenerating Tracts Do Not Provide Strong Guidance Cues for Regenerating Optic Axons. The Journal of neuroscience : the official journal of the Society for Neuroscience. 30(41):13838-13849
Pittman, A.J., Gaynes, J.A., and Chien, C.B. (2010) nev (cyfip2) Is required for retinal lamination and axon guidance in the zebrafish retinotectal system. Developmental Biology. 344(2):784-794
Fredj, N.B., Hammond, S., Otsuna, H., Chien, C.B., Burrone, J., and Meyer, M.P. (2010) Synaptic activity and activity-dependent competition regulates axon arbor maturation, growth arrest, and territory in the retinotectal projection. The Journal of neuroscience : the official journal of the Society for Neuroscience. 30(32):10939-10951
Poulain, F.E., Gaynes, J.A., Hörndli, C.S., Law, M.Y., and Chien, C.B. (2010) Chapter 1 - Analyzing retinal axon guidance in zebrafish. Methods in cell biology. 100:2-26
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 transactions on visualization and computer graphics. 15(6):1489-1496
Kastenhuber, E., Kern U., Bonkowsky, J.L., Chien, C.B., Driever, W., and Schweitzer, J. (2009) Netrin-DCC, Robo-Slit, and heparan sulfate proteoglycans coordinate lateral positioning of longitudinal dopaminergic diencephalospinal axons. The Journal of neuroscience : the official journal of the Society for Neuroscience. 29(28):8914-8926
Willardsen, M.I., Suli, A., Pan, Y., Marsh-Armstrong, N., Chien, C.B., El-Hodiri, H., Brown, N.L., Moore, K.B., and Vetter, M.L. (2009) Temporal regulation of Ath5 gene expression during eye development. Developmental Biology. 326(2):471-481
Veien, E.S., Rosenthal, J.S., Kruse-Bend, R.C., Chien, C.B., and Dorsky, R.I. (2008) Canonical Wnt signaling is required for the maintenance of dorsal retinal identity. Development (Cambridge, England). 135(24):4101-4111
Bonkowsky, J.L., Wang, X., Fujimoto, E., Lee, J.E., Chien, C.B., and Dorsky, R.I. (2008) Domain-specific regulation of foxP2 CNS expression by lef1. BMC Developmental Biology. 8:103
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 (Cambridge, England). 135(17):2865-2871
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 Genetics. 4(7):e1000136
Navankasattusas, S., Whitehead, K.J., Suli, A., Sorensen, L.K., Lim, A.H., Zhao, J., Park, K.W., Wythe, J.D., Thomas, K.R., Chien, C.B., and Li, D.Y. (2008) The netrin receptor UNC5B promotes angiogenesis in specific vascular beds. Development (Cambridge, England). 135(4):659-667
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 : an official publication of the American Association of Anatomists. 236(11):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 : an official publication of the American Association of Anatomists. 236(11):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 arborization and synaptogenesis via Robo2-dependent and -independent pathways. Neuron. 55(2):231-245
Chalasani, S.H., Sabol, A., Xu, H., Gyda, M.A., Rasband, K., Granato, M., Chien, C.B., and Raper, J.A. (2007) Stromal cell-derived factor-1 antagonizes slit/robo signaling in vivo. The Journal of neuroscience : the official journal of the Society for Neuroscience. 27(5):973-980
Ivanov, I.P., Pittman, A.J., Chien, C.B., Gesteland, R.F., and Atkins, J.F. (2007) Novel antizyme gene in Danio rerio expressed in brain and retina. Gene. 387(1-2):87-92
Ekker, S.C., Stemple, D.L., Clark, M., Chien, C.B., Rasooly, R.S., and Javois, L.C. (2007) Zebrafish genome project: bringing new biology to the vertebrate genome field. Zebrafish. 4(4):239-251
Suli, A., Mortimer, N., Shepherd, I., and Chien, C.B. (2006) Netrin/DCC signaling controls contralateral dendrites of octavolateralis efferent neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience. 26(51):13328-13337
Mumm, J.S., Williams, P.R., Godinho, L., Koerber, A., Pittman, A.J., Roeser, T., Chien, C.B., Baier, H., and Wong, R.O. (2006) In vivo imaging reveals dendritic targeting of laminated afferents by zebrafish retinal ganglion cells. Neuron. 52(4):609-621
Zolessi, F.R., Poggi, L., Wilkinson, C.J., Chien, C.B., and Harris, W.A. (2006) Polarization and orientation of retinal ganglion cells in vivo. Neural Development. 1:2
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., 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 (New York, N.Y.). 313(5787):640-644
Bonkowsky, J.L., and Chien, C.B. (2005) Molecular cloning and developmental expression of foxP2 in zebrafish. Developmental dynamics : an official publication of the American Association of Anatomists. 234(3):740-746
Fricke, C., and Chien, C.B. (2005) Cloning of full-length zebrafish dcc and expression analysis during embryonic and early larval development. Developmental dynamics : an official publication of the American Association of Anatomists. 234(3):732-739
Park, K.W., Urness, L.D., Senchuk, M.M., Colvin, C.J., Wythe, J.D., Chien, C.B., and Li, D.Y. (2005) Identification of new netrin family members in zebrafish: Developmental expression of netrin2 and netrin4. Developmental dynamics : an official publication of the American Association of Anatomists. 234(3):726-731
Barresi, M.J., Hutson, L.D., Chien, C.B., and Karlstrom, R.O. (2005) Hedgehog regulated Slit expression determines commissure and glial cell position in the zebrafish forebrain. Development (Cambridge, England). 132(16):3643-3656
Miyasaka, N., Sato, Y., Yeo, S.Y., Hutson, L.D., Chien, C.B., Okamoto, H., and Yoshihara, Y. (2005) Robo2 is required for establishment of a precise glomerular map in the zebrafish olfactory system. Development (Cambridge, England). 132(6):1283-1293
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(6):947-960
Lee, J.S., and Chien, C.B. (2004) When sugars guide axons: insights from heparan sulphate proteoglycan mutants. Nature reviews. Genetics. 5(12):923-935
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. Mechanisms of Development. 121(4):315-324
Hutson, L.D., Jurynec, M.J., Yeo, S.Y., Okamoto, H., and Chien, C.B. (2003) Two divergent slit1 genes in zebrafish. Developmental dynamics : an official publication of the American Association of Anatomists. 228(3):358-369
Rasband, K., Hardy, M., and Chien, C.-B. (2003) Generating X: formation of the optic chiasm. Neuron. 39(6):885-888
Chien, C.-B. and Piotrowski, T. (2002) How the lateral line gets its glia. Trends in neurosciences. 25(11):544-546
Kawahara, A., Chien, C.-B., and Dawid, I.B. (2002) The homeobox gene mbx is involved in eye and tectum development. Developmental Biology. 248(1):107-117
Hutson, L.D. and Chien, C.-B. (2002) Wiring the zebrafish: axon guidance and synaptogenesis. Current opinion in neurobiology. 12(1):87-92
Hutson, L.D. and Chien, C.-B. (2002) Pathfinding and Error Correction by Retinal Axons: The Role of astray/robo2. Neuron. 33(2):205-217
Lee, J.S., Ray, R., and Chien, C.B. (2001) Cloning and expression of three zebrafish roundabout homologs suggest roles in axon guidance and cell migration. Developmental dynamics : an official publication of the American Association of Anatomists. 221(2):216-230
Fricke, C., Lee, J.S., Geiger-Rudolph, S., Bonhoeffer, F., and Chien, C.-B. (2001) astray, a zebrafish roundabout homolog required for retinal axon guidance. Science (New York, N.Y.). 292(5516):507-510
Hutson, L.D. and Chien, C.-B. (2001) Error correction in axon guidance: astray/Robo-2 is required during development of the zebrafish retinotectal pathway. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 15(5):A1071