Hyde Lab: Thomas S. Vihtelic

Research Associate Professor of Biological Sciences

1978	Michigan State University East Lansing, Michigan	B.S. Zoology
1979-80	Department of Physiology, Michigan State University East Lansing, Michigan	Research Associate
1978-82	Michigan State University East Lansing, Michigan	D.V.M.
1982-85	Lakeshore Animal Hospital (Chicago, IL)	Staff Veterinarian
1985-88	Bergman Animal Hospital (Edwardsburg, MI)	Staff Veterinarian
1988-93	University of Notre Dame Notre Dame, Indiana	Ph.D. Molecular Genetics
	under David R. Hyde
1993-94	Department of Ophthalmology and Visual Sciences University of Chicago Chicago, Illinois	Post-doctoral Research Fellow
	under Meredithe L. Applebury
1994-95	Harvard Medical School Boston, Massachusets Massachusetts Eye and Ear Infirmary Howe Laboratory of Retina Molecular Genetics	Instructor of Ophthalmology Research Associate
1995-97	University of Notre Dame Notre Dame, Indiana	Post-doctoral Research Associate
Present	University of Notre Dame, Center for Zebrafish Research	Research Associate Professor

Funded work - COMPLETED
Johnson & Johnson Focused Giving Program
Project Period: 9/1/00 - 8/31/03 - Role: co-PI

Genetic Analysis of Neuronal Degeneration and Regeneration in Zebrafish

The goal of this project was to express GFP specifically in zebrafish rod photoreceptor cells using the zebrafish rod opsin promoter. The stable transgenic lines would then be used in a chemical mutagenesis to identify rod photoreceptor mutants based on the loss of the GFP signal. This would provide a rapid, non-invasive screen compared to performing routine histological analysis of eyes from the thousands of mutagenized progeny. We successfully generated the transgenic line that specifically expresses GFP from the rod opsin promoter (Kennedy et al. (2001) J. Biol. Chem. 276: 14037-14043). The rod opsin promoter line will also be useful to screen for mutants that are defective in photoreceptor regeneration subsequent to light-dependent retinal damage (Vihtelic and Hyde (2000) J. Neurobiol. 44: 289-307).

Funded work - ONGOING
National Institutes of Health - National Eye Institute – RO1 EY014455
Project Period: 04/01/2003 – 02/29/2008 - Role: PI

Identification of Lens Development Genes

The goal of this proposal is to analyze the molecular basis for vertebrate lens development using wild-type and mutant zebrafish. Several zebrafish lens mutants were identified in a chemical mutagenesis screen (Vihtelic, T.S. and D.R. Hyde (2002) Zebrafish mutagenesis yields eye morphological mutants with retinal and lens defects. Vision Research, 42: 535-540). This proposal focuses on the molecular characterization of the arrested lens (arl) mutant (Vihtelic, T.S., Y. Yamamoto, M.T. Sweeney, W.R. Jeffery, and D.R. Hyde (2001) Arrested differentiation and epithelial cell degeneration in zebrafish lens mutants. Developmental Dynamics, 222: 625-636). We will examine if the arl developmental arrest is due to termination of cell proliferation or increased cell death. In addition, the extent of lens cell differentiation will be examined by analyzing the temporal and spatial expression of the zebrafish c-Maf and alphaB-crystallin genes during wild-type and mutant lens development. Also, because mutations in Pitx3 and Foxe3 cause lens vesicle defects in mouse and humans, the zebrafish homologs of these genes will be cloned and characterized. Finally, the arl mutation will be mapped by linkage to simple sequence length polymorphisms (SSLPs) and the arl gene will be identified by positional cloning.

Refereed Manuscripts

1. Hyde, D.R., K.L. Mecklenburg, J.A. Pollock, T.S.Vihtelic and S. Benzer (1990) Twenty Drosophila visual system cDNA clones: one is a homolog of human arrestin. Proc. Natl. Acad. Sci. USA 87:1008-1012.

2. Vihtelic,T.S., D.R. Hyde and J.E. O'Tousa (1991) Isolation and characterization of the Drosophila retinal degeneration-B (rdgB) gene. Genetics 127:761-768.

3. Vihtelic,T.S., M. Goebl, S. Milligan, J.E. O'Tousa and D.R. Hyde (1993) Localization of Drosophila retinal degeneration-B, a membrane-associated phosphatidylinositol transfer protein. J. Cell Biol. 122, No. 5:1013-1022.

4. Hyde, D.R., S. Milligan, and T.S.Vihtelic (1995) The role of the retinal degeneration B protein in the Drosophila visual system. in Degenerative Diseases of the Retina, ed. Robert E. Anderson et al. Plenum Press, New York.

5. Vihtelic, T.S., C.J. Doro and D.R. Hyde (1999) Cloning and characterization of six zebrafish photoreceptor opsin cDNAs and immunolocalization of their corresponding proteins. Vis. Neurosci. 16: 571-585.

6. Lu, D., T.S. Vihtelic, D.R. Hyde, and T. Li (1999) A neuronal-specific mammalian homolog of the Drosophila retinal degeneration B gene with expression restricted to the retina and dentate gyrus. J. Neurosci. 19(17): 7317-7325.

7. Elagin, V.A., R.B. Elagina, C.J. Doro, T.S. Vihtelic, and D.R. Hyde (2000) Cloning and tissue localization of a novel zebrafish rdgB homolog that lacks a phospholipid transfer domain. Vis. Neurosci. 17: 303-311.

8. Vihtelic, T.S. and D.R Hyde (2000) Rod and cone photoreceptor cell death and regeneration in the intense-light-treated adult albino zebrafish (Danio rerio) retina. J. Neurobiology, 44: 289-307.

9. Kennedy, B.N., T.S. Vihtelic, L. Checkley, and D.R. Hyde (2001) Isolation of a zebrafish rod opsin promoter to generate a transgenic zebrafish line expressing EGFP in rod photoreceptors. J. Biol. Chem., 276: 14037-14043.

10. Vihtelic, T.S., Y. Yamamoto, M.T. Sweeney, W.R. Jeffery, and D.R. Hyde. (2001) Arrested differentiation and epithelial cell degeneration in zebrafish lens mutants. Dev. Dynam. 222: 625-636.

11. Vihtelic, T.S. and D.R. Hyde (2002) Zebrafish mutagenesis yields eye morphological mutants with retinal and lens defects. Vision Research, 42: 535-540.

12. Vihtelic, T.S., Y. Yamamoto, S.S. Springer, W.R. Jeffery, and D.R. Hyde (2005) Lens opacity and photoreceptor degeneration in the zebrafish lens opaque mutant. Dev. Dynam. 233(1): 52-65.

13. Shi, X., D.V. Bosenko, N.S. Zinkevich, S. Foley, D.R. Hyde, E.V. Semina, and T.S. Vihtelic (2005) Zebrafish pitx3 is necessary for normal lens and retinal development. Mech Dev, 122(4): 513-527.

14. Wistow, G., K. Wyatt, L. David, C. Gao, O. Bateman, S. Bernstein, S. Tomarev, L. Segovia, C. Slingsby, and T. Vihtelic (2005) gN-crystallin and the evolution of the bg-crystallin superfamily in vertebrates. FEBS J., 272(9): 2276-2291.

15. Vihtelic, T.S., J.M. Fadool, J. Gao, K.A. Thornton, D.R. Hyde and G. Wistow (2005) Expressed sequence tag analysis of zebrafish eye tissues for NEIBank. Mol Vis, 11: 1083-100.

16. Smith, A.A., K. Wyatt, J. Vacha, T.S. Vihtelic, J.S. Zigler Jr., G.J. Wistow and M. Posner (2006) Gene duplication and separation of functions in aB-crystallin from zebrafish (Danio rerio) FEBS J. 273: 481-490.

17. Vihtelic, T.S., J.E. Soverly, S.C. Kassen and D.R. Hyde (2006) Regional differences in photoreceptor cell death and regeneration in light-lesioned albino zebrafish Exp Eye Res, 82: 558-575.

18. Semina, E.V., D.V. Bosenko, N.A. Zinkevich, K.A. Soules, D.R. Hyde, T.S. Vihtelic, G.B. Willer, R.G. Gregg and B.A. Link (2006) Mutations in laminin alpha 1 result in complex, lens-independent ocular phenotypes in zebrafish. Dev Biol, 299: 63-77.

19. Shi, X., Y. Luo, S. Howley, A. Dzialo, S. Foley, D.R. Hyde and T.S. Vihtelic (2006) Zebrafish foxe3: roles in ocular lens morphogenesis through interaction with pitx3. Mech Dev, 123: 761-782.

20. Kassen, S.C., V. Ramanan, J. Montgomery, C. Burket, C-G. Lu, T.S. Vihtelic and D.R. Hyde (2006) Time course analysis of gene expression during light-induced photoreceptor cell death and regeneration in albino zebrafish. J Neurobiol, in press.