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John Dowling, Ph.D.

Professor of Ophthalmology (Neuroscience)

Harvard University FAS Molecular & Cell Biology
Biological Labs
16 Divinity Ave
Cambridge, MA 02138
Telephone: 617 - 495-2245
Fax: 617- 496-3321
Email: dowling@mcb.harvard.edu
Predocs: 0 Postdocs: 7 Completed PhD's: 20

 John Dowling

Zebrafish are highly visual animals, exhibiting robust light responses after just 4 days of development, making them ideal for the genetic analysis of visual behaviors. They have large eyes and are tetrachromatic, possessing ultraviolet- sensitive cones as well as red-, green- and blue-sensitive cones. They also have abundant rods, and both the cones and rods are arranged in a precise mosaic pattern across the retina.

Our group has developed behavioral tests that can be used to uncover visual system specific mutations in zebrafish. One test, based on the optokinetic reflex, enables us to isolate recessive visual system mutations in 5-7 day-old larval fish that appear normal morphologically. We have isolated totally blind, partially blind, color blind and movement-defective mutant fish. A second test, based on the escape response, permits us to isolate dominant mutations in adult fish that demonstrate late onset retinal defects or degenerations.

We also examine young mutagenized fish for developmental eye defects. Eye development is rapid in zebrafish; within 24 hours postfertilization (pf), a well formed eye is present. Differentiation of the neural retina occurs between 1 and 3 days pf, so that by 3 days the retina appears functional.

Other non-visual behaviors can also be elicited easily in zebrafish and hold promise for genetic analysis. For example, zebrafish show robust place conditioning to cocaine. After just one exposure, they repeatedly return to that part of the tank where the exposure first took place. So far, we have isolated three mutants that show altered sensitivity to cocaine. Behavioral tests for memory and learning and auditory responsiveness in zebrafish have been or are being developed in our laboratory.

 

References:

  • Darland, T. and Dowling, J. E. Behavioral screening for cocaine sensitivity in mutagenized zebrafish. Proc. Natl. Acad. Sci., 98, 11691-11696, 2001.
  • Gregg, R. G., Willer, G. B., Fadool, J. M., Dowling, J. E. and Link, B. A. Positional cloning of the young mutation identified an essential role for the Brahma chromatin
  • remodeling complex in mediating retinal cell differentiation, Proc. Natl. Acad. Sci., 100, 6535-6540, 2003.
  • Kainz, P. M., Adolph, A. R., Wong, K. Y. and Dowling, J. E. The lazy eye zebrafish mutation affects Müller glial cells, compromising photoreceptor function and causing partial blindness, J. Comp. Neurol., 463, 265-280, 2003.
  • Wong, K. Y., Cohen, E. D. and Dowling, J. E. Retinal bipolar cell input mechanisms in giant danio: II. Patch-clamp analysis of ON bipolar Neurophysiol. 93, 94-107, 2005.
  • Gross, J. M. and Dowling, J. E. Tbx2b is essential for neuronal differentiation along the dorsal/ventral axis of the zebrafish retina. Proc. Nat. Acad. Sci., 102, 4371-4376, 2005