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Chi-Bin Chien

Associate Professor of Neurobiology and Anatomy

B.A. Johns Hopkins University

Ph.D. California Institute of Technology

Research

References

chi-bin.chien@hsc.utah.edu

 

Research

As the embryonic brain wires itself, a key step is for axons to navigate to their targets. We are studying the cellular and molecular basis of axon guidance, using the zebrafish retinotectal projection as a model. These embryos develop very quickly and are transparent, allowing us to observe cell behavior within the living embryo. Furthermore, we can perturb retinal axons using embryological, genetic, and molecular biological tools. Most importantly, an elegant genetic screen has yielded mutants in ~25 genes that are critical for forming the retinotectal pathway.

We are systematically cloning these mutants and then analyzing the function of the genes. For instance, we found that the astray gene is a homolog of the roundabout (robo) axon guidance receptor, making astray the first known vertebrate robo mutant. Using timelapse analysis of axon behavior, we have shown that astray function is necessary both to prevent and to correct guidance errors during normal development. In addition to robo and slit homologs, we have cloned many other guidance molecules. We can express wildtype and mutant guidance molecules in the visual system, and can make beautiful timelapse movies of retinal growth cones navigating in vivo.

We have recently cloned two other mutants, boxer and nevermind, and are starting to analyze their functions in detail. Intriguingly, astray, boxer, and nevermind are all related to known human disease genes. Finally, we have developed transgenic lines that express green fluorescent protein (GFP) specifically in retinal axons. We have begun next-generation screens using these transgenics.

Confocal projection of wildtype (top) and astray (bottom) zebrafish embryos, injected with diI in the dorsonasal retinal quadrant of the left eye. The wildtype axons project only to contralateral optic tectum, while mutant axons project to both tecta, telencephalon and diencephalon, and display multiple midline crossings.

References