The overall objective of this research proposal is to determine the molecular mechanisms by which photoreceptor cell fate is specified. This will be accomplished by using a combination of molecular biological and genetic techniques. The system of study will be the compound eye of the fruit fly Drosophila melanogaster. In recently published work, we identified and characterized a novel pattern of visual pigment gene expression in the fly eye. By manipulating the eye genetically we have shown that the expression of visual pigment genes in one photoreceptor cell type. It appears that one cell in each ommatidium (R7) adopts one of two different cell fates in a stochastic manner, and then communicates this decision (inductively) to the adjacent R8 cell. These events serve to coordinate the expression of visual pigments in these two cells, and produce two type of optical units within the eye that have distinct spectral sensitivities. In this proposal, we present a series of experiments to rigorously test this model, by examining aspects of opsin gene expression, studying the promoters which regulate their expression, and conducting genetic screens to identify genes which are required for the specification of photoreceptor cell fate and the regulation of opsin gene expression. These studies are of fundamental importance in understanding how the compound eye is formed. The differentiation of photoreceptors into populations having different spectral sensitivities is the basis for color discrimination. Signal trafficking within the nervous as a whole is also dependent upon the generation f diverse neuronal populations having different sensitivities and transmitter phenotypes. Because the fly eye has become a key model system in Developmental Biology, the elucidation of novel signaling and cell-fate determination pathways within this system will serve as a framework to understand more complex developmental events within the nervous system of other organisms.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY012423-03
Application #
6342678
Study Section
Visual Sciences C Study Section (VISC)
Program Officer
Hunter, Chyren
Project Start
2000-01-01
Project End
2003-12-31
Budget Start
2001-01-01
Budget End
2001-12-31
Support Year
3
Fiscal Year
2001
Total Cost
$226,746
Indirect Cost
Name
University of Colorado Denver
Department
Biology
Type
Schools of Medicine
DUNS #
065391526
City
Aurora
State
CO
Country
United States
Zip Code
80045
Szular, Joanna; Sehadova, Hana; Gentile, Carla et al. (2012) Rhodopsin 5- and Rhodopsin 6-mediated clock synchronization in Drosophila melanogaster is independent of retinal phospholipase C-? signaling. J Biol Rhythms 27:25-36
Birkholz, Denise A; Chou, Wen-Hai; Phistry, Meridee M et al. (2009) rhomboid mediates specification of blue- and green-sensitive R8 photoreceptor cells in Drosophila. J Neurosci 29:2666-75
Birkholz, Denise A; Chou, Wen-Hai; Phistry, Meridee M et al. (2009) Disruption of photoreceptor cell patterning in the Drosophila Scutoid mutant. Fly (Austin) 3:253-62
Bell, Melanie L; Earl, James B; Britt, Steven G (2007) Two types of Drosophila R7 photoreceptor cells are arranged randomly: a model for stochastic cell-fate determination. J Comp Neurol 502:75-85
Earl, James B; Britt, Steven G (2006) Expression of Drosophila rhodopsins during photoreceptor cell differentiation: insights into R7 and R8 cell subtype commitment. Gene Expr Patterns 6:687-94