PICTURE

James M. Fadool, Ph.D.

Assistant Professor

A.B., Albion College, 1985
Ph.D., Michigan State University, 1992
Post Doc, University of Florida, 1992-1994
Post Doc, Harvard University, 1994-1997

Embryology, Development of the Visual System, Zebrafish Genetics



Department of Biological Science
Florida State University
235 BRF
Tallahassee, FL 32306-4340
TEL: 850-644-3550

E-MAIL: jfadool@bio.fsu.edu
Back to JFadool at FSU


Honors/Awards

Webster Merit Scholarship, Albion College
NIH/NEI Postdoctoral Trainee, The Whitney Laboratory, University of Florida, 1992-1993.
NIH/NEI Postdoctoral Fellow, Molecular and Cellular Biology, Harvard University, 1994-1997.


retina

Research/Interests

Our research goal is to identify fundamental mechanisms governing the development of the vertebrate central nervous system through systematic genetic and molecular analyses. We concentrate our efforts on the neural retina, the photosensitive lining of the back of the eye. Like many regions of the brain, the anatomical organization, biochemical processes and gene expression patterns in the retina are conserved in virtually all vertebrate species. Our hope is that an understanding of the pathways that regulate gene expression and ultimately cellular differentiation in the neural retina will aid in the identification and management of genetic disorders affecting the visual system such as retinitis pigmentosa, macular degeneration and glaucoma.

As a genetic model of vertebrate development, we utilize the zebrafish (Danio rerio), a small fresh water teleost. To uncover novel genes or novel gene functions in pathways involved in eye development, a systematic screen for mutations was conducted in the laboratory of Professor John E. Dowling, at Harvard University (Dev. Genetics 20:288 295). We recovered numerous mutations affecting the development of the eye. The phenotypes range from patterning defects, loss of specific cells types in the retina to degenerations of the retina. These mutations provide a resource to genetically dissect the biochemical pathways involved in the development and function of the affected systems. The characterization of the existing mutations and the search for new mutations are continuing in my laboratory.

The second project in the lab takes advantage of our recently developed methodology for transgenesis as a method to identify genes important to zebrafish development. The novel method utilizes a transposable elements, or "jumping gene" as a universal vector for transgenic fish. Transposons are naturally occurring genetic elements capable of moving from one chromosomal location to another. We have demonstrated that the mariner element, from the fruit fly, Drosophila mauritiana (P.N.A.S. USA, 1998), can be successfully employed to generate transgenic zebrafish. The demonstration that a transposon from the fruit fly can function in such a diverse organism as the zebrafishin in itself is a very exciting finding. The current objective is to apply this novel technique, to tag genes in the zebrafish and screen for transcriptionally active regions of the genome. We recently described a novel cellular arrangement to the photoreceptors of the zebrafish retina using a transgenic line expressing fluorescent reporter genes (eGFP) under the control of cell specific promoter (Dev Biol, 2003). Taking advantage of the optical clarity of the zebrafish embryo and recent advances in microscopy and analysis tools, we identified a mosaic organization to the rod photoreceptors. We continue to take full advantage of this and other transgenic lines as powerful experimental models to screen for mutations and chemicals to identify pathways essential for cellular differentiation and patterning.

Transposon Strategy


transgenic

Selected Publications

Fadool, J.M., Brockerhoff, S.E., Hyatt, G.A. and Dowling, J.E. (1997) Mutations affecting eye morphology in the developing zebrafish (Danio rerio). Dev. Genetics. 20:288-295. ABSTRACT Fadool, J.M., Hartl, D.L. and Dowling, J.E. (1998) Transposition of the mariner element from Drosophila mauritiana in zebrafish (Danio rerio). Proc. Natl. Acad. Sci. USA 95:5182-5186.ABSTRACT Link, B.A., Fadool, J.M., Malicki, J., Dowling, J.E. (2000) The zebrafish young mutation acts non-cell-autonomously to uncouple differentiation from specification for all retinal cells. Development 127:2177-2188.ABSTRACT Peterson, R.E., Fadool, J.M., McClintock, J. and Linser, P.J. (2001) Muller cell differentiation in the zebrafish neural retina: Evidence of distinct early and late stages of cellular maturation. J. Comp. Neurol. 429(4):530-540. ABSTRACT Fadool, J.M. (2001) Understanding retinal cell fate determination through genetic manipulations. Prog Brain Res. 131:541-54. McCune, A.R., Fuller, R.C., Aquilina, A.A., Dawley, R.M., Fadool, J.M., Houle, D., Travis, J., Kondrashov, A.S. (2002) A low genomic number of recessive lethals in natural populations of bluefin killifish and zebrafish. Science 296:2398-401. Abstract Gregg, R.G., Willer, G.B., Fadool, J.M., Dowling, J.E., Link, B.A. (2003) Positional cloning of the young mutation identifies an essential role for the Brahma chromatin remodeling complex in mediating retinal cell differentiation. Proc Natl Acad Sci U S A. 100:6535-40. Abstract Fadool, J.M.. (2003) Development of a rod photoreceptor mosaic revealed in transgenic zebrafish. Dev Biol. 258: 277-90. Abstract Ochrietor, J.D., Moroz, T.P., van Ekeris, L., Clamp, M.F., Jefferson, S.C., deCarvalho, A.C., Fadool, J.M., Wistow, G., Muramatsu, T., Linser, P.J. (2003) Retina-specific expression of 5A11/Basigin-2, a member of the immunoglobulin gene superfamily. Invest Ophthalmol Vis Sci. 44:4086-96. Abstract Fadool, J.M.. (2003) Rod photoreceptor cell development in the teleost as a model for neural stem cells. Exp. Neurol. (in press).

GFP expression in Transgenic Zebrafish Driven by Xenopus Rhodopsin Promotor

Photoreceptor Cell Mosaic eGFP Expression 80 hpf
gfppineal gfprods
Vector kindly provided by David Papermaster, UCONN
Department of Biological Science
Florida State University