James M. Fadool

Assistant Professor Ph.D. (1992) Michigan State University

Office: 235 BRF
Telephone: (850) 644-3550
Fax: (850) 644-0989
jfadool@bio.fsu.edu
Zebrafish Lab Home Page

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 Publications

	Aggarwal, 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.