Over the next 5 years, the main objective of this project will be to isolate and analyze visual system mutations in zebrafish. Mutations are induced in zebrafish by exposing males to ethylnitrosurea. Dominant mutations are looked for in Fl generation fish, whereas recessive mutations are isolated from F3 generation fish bred from F2 generation siblings. Both developmental and functional mutations will be sought, the latter by the use of visual behavioral tests developed in our laboratory. After mutants are isolated, they are characterized by light and electron microscopy, immunohistochemistry, in situ hybridization, electroretinography and mosaic analysis. A particular thrust of the next few years of the project will be to map mutated genes and, in certain cases, to clone and sequence the mutated genes. Another aspect of this research project is to study normal retinal development in zebrafish. The focus for the next several years will be on the role of retinoic acid in establishing the dorsal-ventral axis in the eye. To this end, we will examine the temporal and spatial expression patterns of retinoic acid synthetic and degrading enzymes in the zebrafish eye.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY000811-34
Application #
6832768
Study Section
Visual Sciences C Study Section (VISC)
Program Officer
Hunter, Chyren
Project Start
1976-12-01
Project End
2006-11-30
Budget Start
2004-12-01
Budget End
2005-11-30
Support Year
34
Fiscal Year
2005
Total Cost
$499,824
Indirect Cost
Name
Harvard University
Department
Microbiology/Immun/Virology
Type
Schools of Arts and Sciences
DUNS #
082359691
City
Cambridge
State
MA
Country
United States
Zip Code
02138
Wasfy, Meagan M; Matsui, Jonathan I; Miller, Jessica et al. (2014) myosin 7aa(-/-) mutant zebrafish show mild photoreceptor degeneration and reduced electroretinographic responses. Exp Eye Res 122:65-76
Moyano, Miguel; Porteros, Angel; Dowling, John E (2013) The effects of nicotine on cone and rod b-wave responses in larval zebrafish. Vis Neurosci 30:141-5
Li, Yong N; Tsujimura, Taro; Kawamura, Shoji et al. (2012) Bipolar cell-photoreceptor connectivity in the zebrafish (Danio rerio) retina. J Comp Neurol 520:3786-802
Le, Hong-Gam T; Dowling, John E; Cameron, D Joshua (2012) Early retinoic acid deprivation in developing zebrafish results in microphthalmia. Vis Neurosci 29:219-28
Hensley, Monica R; Emran, Farida; Bonilla, Sylvia et al. (2011) Cellular expression of Smarca4 (Brg1)-regulated genes in zebrafish retinas. BMC Dev Biol 11:45
Stujenske, Joseph M; Dowling, John E; Emran, Farida (2011) The bugeye mutant zebrafish exhibits visual deficits that arise with the onset of an enlarged eye phenotype. Invest Ophthalmol Vis Sci 52:4200-7
Emran, Farida; Rihel, Jason; Adolph, Alan R et al. (2010) Zebrafish larvae lose vision at night. Proc Natl Acad Sci U S A 107:6034-9
Li, Yong N; Matsui, Jonathan I; Dowling, John E (2009) Specificity of the horizontal cell-photoreceptor connections in the zebrafish (Danio rerio) retina. J Comp Neurol 516:442-53
Emran, Farida; Rihel, Jason; Dowling, John E (2008) A behavioral assay to measure responsiveness of zebrafish to changes in light intensities. J Vis Exp :
Kojima, Daisuke; Torii, Masaki; Fukada, Yoshitaka et al. (2008) Differential expression of duplicated VAL-opsin genes in the developing zebrafish. J Neurochem 104:1364-71

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