Office: 235 BRF
Telephone: (850) 644-3550
Fax: (850) 644-0989
Zebrafish Lab Home Page
Developmental Genetics and Degenerative Disease of the Visual System.
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 hypothesis 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.
Both of the projects in the laboratory utilize the zebrafish (Danio rerio), a small fresh water teleost, as a genetic model of neural development. Numerous mutations affecting the development of the eye were recovered in a third generation screen of chemically mutagenized zebrafish. The phenotypes range from patterning defects, loss of specific cells types in the retina to degenerations of the retina. Once identified, the mutations are characterized through molecular, biochemical, histological and physiological analyses. These mutations provide in roads to begin a systematic genetic dissection of the biochemical pathways involved in the development and function of the visual system. 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, can be successfully employed to generate transgenic zebrafish. This demonstration that a transposon from Drosophila can function in such a diverse organism as the zebrafish is in itself 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.
Selected PublicationsAggarwal, S.K. and Fadool, J.M. (1993) Cisplatin and carboplatin induced changes in the neurohypophysis and parathyroid, and their role in nephrotoxicity. Anti-Cancer Drugs 4:149-162. ABSTRACT Fadool, J.M. and Linser, P.J. (1993) The 5A11/HT7 antigen is a cell recognition molecule specifically involved in neuronal-glial interactions in the avian neural retina.Dev.Dynamics 196:252-262. ABSTRACT Fadool, J.M. and Linser, P.J. (1993) Differential glycosylation of the 5A11/HT7 antigen by neural retina and epithelial tissues in the chicken. J. Neurochem. 60:1354-1364. ABSTRACT Fadool, J.M. and Linser, P.J. (1994) Spatial and temporal expression of the 5A11/HT7 antigen in the chick embryo: Association with morphogenetic events and tissue maturation. Roux's Archives of Dev. Biol. 203:328-339. ABSTRACT Fadool, J.M. and Linser, P.J. (1996) Evidence for formation of multimeric forms of the 5A11/HT7 antigen. Biochem. Byophys. Res. Comm. 229:280-286. ABSTRACT Hyatt, G.A, Schmitt, E.A., Fadool, J.M. and Dowling, J.E. (1996) Retinoic acid alters photoreceptor development in vivo. Proc. Natl. Acad. Sci. USA 93:13298-13302. ABSTRACT 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. (in press) Muller cell differentiation in the zebrafish neural retina: Evidence of distinct early and late stages of cellular maturation. J. Comp Neurol.