Understanding the signaling mechanisms that pattern and maintain the human eye are critically important to the medical community. A considerable amount of work is directed to understanding the pattern formation that occurs in the vertebrate eye, with the mouse being the standard model organism. Although completely unexpected, over the last 10 years it has become increasingly evident that the fly eye shares many structural and patterning features with the vertebrate eye. Thus, the fly can be considered another model organism for studying vertebrate eye development. Work in this lab has examined how signals from the tissue directly surrounding fly retina induce peripheral specializations necessary for the functioning eye. Recently, the same phenomenon was shown to occur in the mouse, using the same class of signaling molecules. Here, Wnt signals from the tissue directly adjacent to the retina direct the formation of the ciliary body and the iris. Our goals here are to examine in fine detail the patterning mechanisms by which the peripheral specializations are produced in the fly eye. We will use fly genetics, molecular biology, histology and biochemistry to determine the exact nature of the signals released that organize the peripheral specializations. We will elucidate the genes or proteins that are specifically turned on in the peripheral regions, and how they interact to direct the differentiation of the specialized structures. The results accruing from this work can then be taken and examined in the mouse to further our general understanding of retinal differentiation and its implications for human disease and vision.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY012536-10
Application #
7585218
Study Section
Biology and Diseases of the Posterior Eye Study Section (BDPE)
Program Officer
Mariani, Andrew P
Project Start
1999-05-01
Project End
2012-03-31
Budget Start
2009-04-01
Budget End
2010-03-31
Support Year
10
Fiscal Year
2009
Total Cost
$509,243
Indirect Cost
Name
Columbia University (N.Y.)
Department
Genetics
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Kumar, Sudha R; Patel, Hina; Tomlinson, Andrew (2015) Wingless mediated apoptosis: How cone cells direct the death of peripheral ommatidia in the developing Drosophila eye. Dev Biol 407:183-94
Mavromatakis, Yannis Emmanuel; Tomlinson, Andrew (2013) Switching cell fates in the developing Drosophila eye. Development 140:4353-61
Tomlinson, Andrew (2012) The origin of the Drosophila subretinal pigment layer. J Comp Neurol 520:2676-82
Mavromatakis, Yannis Emmanuel; Tomlinson, Andrew (2012) The role of the small GTPase Rap in Drosophila R7 photoreceptor specification. Proc Natl Acad Sci U S A 109:3844-9
Tomlinson, Andrew; Mavromatakis, Yannis Emmanuel; Struhl, Gary (2011) Three distinct roles for notch in Drosophila R7 photoreceptor specification. PLoS Biol 9:e1001132
Wang, Ji-Wu; Brent, Jonathan R; Tomlinson, Andrew et al. (2011) The ALS-associated proteins FUS and TDP-43 function together to affect Drosophila locomotion and life span. J Clin Invest 121:4118-26
Sato, Atsushi; Tomlinson, Andrew (2007) Dorsal-ventral midline signaling in the developing Drosophila eye. Development 134:659-67
Katanaev, Vladimir L; Tomlinson, Andrew (2006) Dual roles for the trimeric G protein Go in asymmetric cell division in Drosophila. Proc Natl Acad Sci U S A 103:6524-9
Tomlinson, A; Struhl, G (2001) Delta/Notch and Boss/Sevenless signals act combinatorially to specify the Drosophila R7 photoreceptor. Mol Cell 7:487-95
Tomlinson, A; Struhl, G (1999) Decoding vectorial information from a gradient: sequential roles of the receptors Frizzled and Notch in establishing planar polarity in the Drosophila eye. Development 126:5725-38