Over the past several years our research on determination of the retina and lens has led us to a revised and refined view of how these tissues are formed during development. During the period of proposed support our first goal will be to fill in key gaps that still remain in our understanding of the inductive interactions controlling the formation of these tissues. Much of the proposed work will utilize examination of Xenopus embryos, which provide an excellent system for manipulating tissues during early development. In addition we will undertake studies of mouse embryonic lens determination because of the availability of genetic information that will be of great help in understanding how this process is controlled. Foremost among our studies will be examination of tissue interactions responsible for the phenotype (blocked retina and lens formation) of Small-eye mice, now known to be deficient in the homeobox gene Pax-6. Because this is the same gene responsible for the human syndrome Aniridia, it is expected that our work will be of significant value in understanding the origin of this clinical problem. The second phase of our work will focus on the signal transduction mechanisms responsible for retina and lens formation. With information in hand about tissue interactions, we can define the likely source of signals and propose to attempt to identify them. In addition we will plan to investigate what receptors and second messenger systems control retina and lens determination, primarily by using a number of existing dominant negative constructs for key signal transduction elements.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY006675-13
Application #
2710932
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1986-08-01
Project End
2000-11-30
Budget Start
1998-08-01
Budget End
2000-11-30
Support Year
13
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Virginia
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
001910777
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
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Ogino, Hajime; Ochi, Haruki; Uchiyama, Chihiro et al. (2012) Comparative genomics-based identification and analysis of cis-regulatory elements. Methods Mol Biol 917:245-63
Jin, Hong; Fisher, Marilyn; Grainger, Robert M (2012) Defining progressive stages in the commitment process leading to embryonic lens formation. Genesis 50:728-40
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Ogino, Hajime; Fisher, Marilyn; Grainger, Robert M (2008) Convergence of a head-field selector Otx2 and Notch signaling: a mechanism for lens specification. Development 135:249-58
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Gonzalez-Fernandez, F; Kittredge, K L; Rayborn, M E et al. (1993) Interphotoreceptor retinoid-binding protein (IRBP), a major 124 kDa glycoprotein in the interphotoreceptor matrix of Xenopus laevis. Characterization, molecular cloning and biosynthesis. J Cell Sci 105 ( Pt 1):7-21
Saha, M S; Michel, R B; Gulding, K M et al. (1993) A Xenopus homebox gene defines dorsal-ventral domains in the developing brain. Development 118:193-202

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