Cell-fate specification plays an essential role in the ultimate function of the nervous system. Generation of diverse cell populations and the regulation of their precise placement and connectivity patterns establishes neural networks capable of detecting, processing and sending complex signals. Cell identity, position and connectivity are especially important in sensory systems because of the added complexity of spatial information that must be detected and encoded. High-resolution sampling of visual space by the retina demands a dense array of photoreceptor cells sensitive to a wide dynamic range of light intensities. Moreover, color vision requires photoreceptor cells having different spectral sensitivities in addition to a precise retinotopic map. Currently, little is known about the generation of photoreceptor cell diversity or the specification of different spectral types. Drosophila melanogaster is capable of color vision and is a useful experimental system for examining the developmental programs that produce photoreceptor cells having different color sensitivities. We have found that a very specific inductive signal between adjacent photoreceptor cells coordinates their fates and color sensitivities. We have identified a large group of genes that influence this inductive signal. These genes include members of the Epidermal Growth Factor Receptor, nephrin related immunoglobulin superfamily (IgSF), and Notch signaling pathways.
The aim of this proposal is to determine how the individual members of these signal transduction pathways function to establish photoreceptor cell-type adjacency and pairing, and to examine how these pathways interact in a coordinated way to regulate the inductive signal between adjacent photoreceptors. This work will provide a better understanding for how specific developmental signals operate during eye development and establish the patterned photoreceptor cell mosaic that is capable of color vision.

Public Health Relevance

In our previous work, we have identified a group of genes that are required to establish the precise cell-cell adjacency of the R7 and R8 cell types in pale and yellow ommatidia. The purpose of this proposal is to define how each of the individual genes function in this process and to determine how they interact with each other overall. Because the molecular mechanisms that regulate eye development in different organisms are highly conserved, we believe that using Drosophila melanogaster as a model system to identify and characterize the genes responsible for photoreceptor cell patterning will provide important information that will be relevant to retina development in general. Furthermore, we believe that our analyses of the integration of multiple signal transduction pathways will also provide important insights that will be relevant to a variety of developmental and signaling processes in both health and disease.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Biology and Diseases of the Posterior Eye Study Section (BDPE)
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Neuhold, Lisa
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University of Colorado Denver
Schools of Medicine
United States
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Powell, Davalyn R; Blasky, Alex J; Britt, Steven G et al. (2013) Riding the crest of the wave: parallels between the neural crest and cancer in epithelial-to-mesenchymal transition and migration. Wiley Interdiscip Rev Syst Biol Med 5:511-22
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