The development and growth of the vertebrate eye must be perfectly coordinated in order to transmit correct visual images to the brain. The lens is responsible in part for coordinating eye growth but the underlying molecular and cellular mechanisms are unknown. We will investigate this problem in Astyanax mexicanus, a teleost species consisting of an eyed surface dwelling form (surface fish) and a blind cave-dwelling form (cavefish). Eye primordia are initially formed during cavefish development but subsequently arrest and degenerate, resulting in a blind adult. The first tissue to degenerate is the lens. Remarkably, transplanting a surface fish embryonic lens into a cavefish optic cup can restore a complete eye in adult cavefish. We propose to study the molecular and cellular basis of lens regulation of eye growth and development in Astyanax, which is uniquely suited for lens manipulations. The first three specific aims are designed to determine the cellular events underlying the arrest of retinal, corneal, and scleral differentiation in cavefish and how the lens modulates these events. In these aims we will combine lens transplantation methods with specific molecular markers for retina, cornea, and sclera development. The fourth specific aim is to identify candidate genes encoding lens-signaling factors affecting the development of other eye parts. The genes will be obtained by a subtractive hybridization using cDNA libraries obtained from isolated surface fish and cavefish lenses. The fifth specific aim is to determine the role of the candidate genes in lens degeneration and lens-regulated development of other eye tissues. This will be done by loss-of-function and gain of function studies, as well as by capitalizing on specific properties of the candidate genes. We expect this research to provide new insights into lens signaling processes and fill a major gap in our understanding of both normal and abnormal eye development.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY014619-04
Application #
7077653
Study Section
Special Emphasis Panel (ZRG1-VISA (01))
Program Officer
Araj, Houmam H
Project Start
2003-08-01
Project End
2008-05-31
Budget Start
2006-06-01
Budget End
2007-05-31
Support Year
4
Fiscal Year
2006
Total Cost
$286,736
Indirect Cost
Name
University of Maryland College Park
Department
Biology
Type
Schools of Earth Sciences/Natur
DUNS #
790934285
City
College Park
State
MD
Country
United States
Zip Code
20742
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Yoshizawa, Masato; Robinson, Beatriz G; Duboué, Erik R et al. (2015) Distinct genetic architecture underlies the emergence of sleep loss and prey-seeking behavior in the Mexican cavefish. BMC Biol 13:15
Ma, Li; Jeffery, William R; Essner, Jeffrey J et al. (2015) Genome editing using TALENs in blind Mexican Cavefish, Astyanax mexicanus. PLoS One 10:e0119370
Espinasa, Luis; Bibliowicz, Jonathan; Jeffery, William R et al. (2014) Enhanced prey capture skills in Astyanax cavefish larvae are independent from eye loss. Evodevo 5:35
McGaugh, Suzanne E; Gross, Joshua B; Aken, Bronwen et al. (2014) The cavefish genome reveals candidate genes for eye loss. Nat Commun 5:5307
Ma, Li; Parkhurst, Amy; Jeffery, William R (2014) The role of a lens survival pathway including sox2 and ?A-crystallin in the evolution of cavefish eye degeneration. Evodevo 5:28
Yoshizawa, Masato; Jeffery, William R; van Netten, Sietse M et al. (2014) The sensitivity of lateral line receptors and their role in the behavior of Mexican blind cavefish (Astyanax mexicanus). J Exp Biol 217:886-95
Kowalko, Johanna E; Rohner, Nicolas; Rompani, Santiago B et al. (2013) Loss of schooling behavior in cavefish through sight-dependent and sight-independent mechanisms. Curr Biol 23:1874-83
O'Quin, Kelly E; Yoshizawa, Masato; Doshi, Pooja et al. (2013) Quantitative genetic analysis of retinal degeneration in the blind cavefish Astyanax mexicanus. PLoS One 8:e57281
Yoshizawa, Masato; O'Quin, Kelly E; Jeffery, William R (2013) Evolution of an adaptive behavior and its sensory receptors promotes eye regression in blind cavefish: response to Borowsky (2013). BMC Biol 11:82

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