Chi-Bin Chien
Professor of Neurobiology and Anatomy
B.A. Johns Hopkins University
Ph.D. California Institute of Technology
Research
For the developing brain to function properly, it must acquire the correct shape, pattern itself, and produce differentiated neurons, which then extend axons and form synaptic connections with each other. We study the cellular and molecular bases of neural development, using the zebrafish visual system as a model. These embryos develop quickly and are transparent, allowing us to observe cell behavior within the living embryo. Furthermore, we can perturb retinal development and axon guidance using embryological, genetic, and molecular biological tools.
We have cloned several axon guidance mutants and are intensively studying how they function in axons in vivo. For instance, we find that the Astray/Robo2 axon guidance receptor helps to guide retinal axons in at least three distinct guidance choices along their pathway. In the optic chiasm, timelapse analysis shows that Robo2 helps both to prevent and to correct guidance errors. We are currently studying guidance of axons in the optic tract by Slit ligands; signaling downstream of Robo2; and possible roles of robo2 alternative splicing.
Recently we have started expanding 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.

Confocal projection of wildtype (top) and astray mutant (bottom) zebrafish embryos, injected with diI in the dorsonasal quadrant of the left eye. The wildtype axons project only to contralateral optic tectum, while mutant axons make drastic pathfinding errors, projecting to both tecta, telencephalon and diencephalon, with multiple midline crossings.
References
1. Campbell DS, Stringham SA, Timm A, Xiao T, Law MY, Baier H, Nonet ML, Chien CB (2007) Slit1a inhibits retinal ganglion cell arborisation and synaptogenesis via Robo2-dependent and -independent pathways. Neuron 55:241-35
2. Wilson BD*, Ii M*, Park KW*, Suli A*, Sorensen LK, Larrieu-Lahargue F, Urness LD, Suh W, Asai J, Kock GAH, Thorne T, Silver M, Thomas KR, Chien CB, Losordo DW, Li DY (2006) Netrins promote developmental and therapeutic angiogenesis. Science 313:640-4 *=equal contributions
3. Lee JS, von der Hardt S, Rusch MA, Stringer SE, Stickney HL, Talbot WS, Geisler R, Nüsslein-Volhard C, Selleck SB, Chien CB*, Roehl H* (2004) Axon sorting in the optic tract requires HSPG synthesis by ext2 ( dackel ) and extl3 ( boxer ). Neuron 44:947-960 *=equal contributions
4. Lee JS, Chien CB (2004) When sugars guide axons: new insights from heparan sulphate proteoglycan mutants. Nature Reviews Genetics 5:923-935
5. Hutson LD, Chien CB (2002) astray/robo2 is required for guidance and error correction in zebrafish retinal axons. Neuron 33:205-217
6. Hutson LD, Chien CB (2002) Wiring the zebrafish: axon guidance and synaptogenesis. Current Opinion in Neurobiology 12:87-92
7. Fricke C, Lee JS, Bonhoeffer F, Geiger-Rudolph S, Chien CB (2001) astray , a zebrafish Roundabout required for retinal axon pathfinding . Science 292:507-510
8. Lee JS, Ray R, Chien CB (2001) Cloning and expression of three zebrafish Roundabout homologs suggest roles in axon guidance and cell migration. Developmental Dynamics 221:216-230
9. Chien CB (1998) Why does the growth cone cross the road? Neuron 20:3-6
10. Chien CB (1996) PY in the fly: receptor-like tyrosine phosphatases in axonal pathfinding. Neuron 16:1065-1068
11. Chien CB, Rosenthal DE, Harris WA, Holt CE (1993) Navigational errors made by growth cones without filopodia in the embryonic Xenopus brain. Neuron 11:237-251


