Chi-Bin Chien, Ph.D.

Associate Professor of Neurobiology and Anatomy (b. 1965); 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. Email: Office Phone: 801-585-1701 Visit the Chien Lab web site

Many of the signaling molecules that are critical for development have now been identified: for instance, guidance ligands and receptors during axon and vascular guidance, and morphogens and transcription factors during embryonic patterning. It is much less clear how these molecules function in cells during development, and furthermore how multiple signaling pathways are orchestrated as the embryo develops. The zebrafish Danio rerio is an ideal system for understanding how genetic and molecular mechanisms control cell behavior in vivo.

Dr. Chien's lab concentrates on three different problems during development:

1. Axon guidance in the retinotectal system. We have identified many of the key molecules that control retinal axon guidance, sorting, and branching, including Slits, Robos, heparan sulfate proteoglycans (HSPGs), and the cytoplasmic protein Cyfip2. We are developing methods to perturb these molecules' function in vivo, including local heat shock and in vivo electroporation, and then to image the resulting effects on retinal axon behavior, both in fixed tissue and in timelapse.
2. Vascular guidance in the zebrafish trunk. In the last few years it has become clear that growing blood vessels use many of the same cues as growing axons. In collaboration with Dean Li's lab, we recently showed that Netrins act as attractants to guide the growing parachordal vessels (PAVs) in the zebrafish trunk. We are analyzing when and where Netrin acts, and what receptors are used.
3. Morphogenesis and patterning of the eye. We are interested in two questions: how the optic cup evaginates, rotates, and invaginates to form the neural retina, and how at the same time it becomes patterned along the dorsoventral (D-V) axis, eventually leading to topographically-correct projections to the optic tectum. We are using four-dimensional timelapse microscopy to analyze patterns of mitosis, cell shape change, and cell movement during eye morphogenesis. We are using combinations of mutants, antisense morpholinos, and conditional gene expression to analyze the mechanisms that control D-V retinal patterning. We are also carrying out a forward-genetic screen to look for mutants in morphogenesis and D-V patterning.

We are also developing a variety of techniques to aid us in these studies, including: transgenic lines for labeling the visual system; methods for live imaging of growth cones and vasculatuare; the Tol2kit, a system for rapidly building Tol2 transposon-based transgenesis constructs; and a method for local induction of transgenes driven by the heatshock promoter.

Search Pubmed for Chi-Bin Chien's lab publications

Selected Publications

A Suli, N Mortimer, I Shepherd, CB Chien (2006) Netrin/DCC signaling controls contralateral dendrites of octavolateralis efferent neurons. Journal of Neuroscience, 26:13328-37.

BD Wilson*, M Ii*, KW Park*, A Suli*, LK Sorensen, F Larrieu-Lahargue, LD Urness, W Suh, J Asai, GAH Kock, T Thorne, M Silver, KR Thomas, CB Chien, DW Losordo, and DY Li (2006). Netrins promote developmental and therapeutic angiogenesis. Science, 313:640-4.
*=equal contributions.

C Fricke and CB Chien (2005) Cloning of full-length zebrafish dcc and expression analysis during embryonic and early larval development. Developmental Dynamics, 234:732-9.

JL Bonkowsky and CB Chien (2005) Molecular cloning and developmental expression of foxP2 in zebrafish. Developmental Dynamics, 234:740-6.

JS Lee, S von der Hardt, MA Rusch, SE Stringer, HL Stickney, WS Talbot, R Geisler, C Nüsslein-Volhard, SB Selleck, CB Chien*, and H Roehl* (2004) Axon sorting in the optic tract requires HSPG synthesis by ext2 (dackel) and extl3 (boxer). Neuron, 44:947-960.
*=equal contributions.

LD Hutson and CB Chien (2002) astray/robo2 is required for guidance and error correction in zebrafish retinal axons. Neuron 33:205-217.

C Fricke, JS Lee, F Bonhoeffer, S Geiger-Rudolph, and CB Chien (2001) astray, a zebrafish Roundabout required for retinal axon pathfinding. Science 292:507-510.

Reviews

JS Lee and CB Chien (2004). When sugars guide axons: new insights from heparan sulphate proteoglycan mutants. Nature Reviews Genetics, 5:923-935.

LD Hutson, DS Campbell, and CB Chien (2004) Analyzing axon guidance in the zebrafish retinotectal system. Methods in Cell Biology, 76:13-35.

K Rasband, M Hardy, CB Chien (2003) Generating X: formation of the optic chiasm (minireview). Neuron, 39:885-888.

Collaborative manuscripts

S Chalasani, A Sabol, H Xu, M Gyda, K Rasband, M Granato, CB Chien, J Raper (2007) Stromal Cell Derived Factor-1 (SDF-1) antagonizes Slit/Robo signaling in vivo. Journal of Neuroscience, 27:973-80

KW Park, LD Urness, MM Senchuk, CJ Colvin, JD Wythe, CB Chien, and DY Li. (2005) Identification of new Netrin family members in zebrafish: Developmental expression of netrin2 and netrin4. Developmental Dynamics, 234: 726-31.

MJF Barresi, LD Hutson, CB Chien, and RO Karlstrom (2005) Hedgehog regulated Slit expression determines commissure and glial cell position in the zebrafish forebrain. Development, 132:3643-56.

N Miyasaka, Y Sato, SY Yeo, LD Hutson, CB Chien, H Okamoto, and Y Yoshihara (2005) Robo2 mediates the formation of an initial axon scaffold essential for establishment of precise glomerular map in the zebrafish olfactory system. Development, 132:1283-93.

KW Park, CM Morrison, LK Sorensen, CA Jones, Y Rao, CB Chien, JY Wu, LD Urness, and DY Li (2003) Robo4 is a vascular-specific receptor that inhibits endothelial migration. Developmental Biology, 261:251-267.

Textbook Chapter

CB Chien (2005). "Axon and dendrite guidance." In Developmental Neurobiology, 4th edition, editors MS Rao and M Jacobson. Kluwer/Plenum.