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Britt, S. G.

Publications and source records attributed to Britt, S. G..

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Identification of genes involved in the differentiation of R7y and R7p photoreceptor cells in Drosophila

The R7 and R8 photoreceptor cells of the Drosophila compound eye mediate color vision. Throughout the majority of the eye, these cells occur in two principal types of ommatidia. Approximately 35% of ommatidia are of the pale type and express Rh3 in R7 cells and Rh5 in R8 cells. The remaining 65% are of the yellow type and express Rh4 in R7 cells and Rh6 in R8 cells. The specification of an R8 cell in a pale or yellow ommatidium depends on the fate of the adjacent R7 cell. However, pale and yellow R7 cells are specified by a stochastic process that requires the genes spineless, tango and klumpfuss. To identify additional genes involved in this process we performed a genetic screen using a collection of 480 P{EP} transposon insertion strains. We identified genes that when inactivated and/or ectopically expressed in R7 cells resulted in a significantly altered percentage of Rh3 expressing R7 cells (Rh3%) from wild-type. 53 strains resulted in altered Rh3% in the heterozygous inactivation arm of the screen. 36 strains resulted in altered Rh3% in the ectopic expression arm of the screen, where the P{EP} insertion strains were crossed to a sevEP-GAL4 driver line. 4 strains showed differential effects between the two screens. Analyses of these results suggest that R7 cell fate specification is sensitive to perturbations in transcription, growth inhibition, glycoprotein ligand binding, WNT signaling, ubiquitin protease activity and Ser/Thr kinase activity, among other diverse signaling and cell biological processes.

genetics

Drosophila R8 photoreceptor cell subtype specification requires Notch and hibris.

Cell differentiation and cell fate determination in sensory systems are essential for stimulus discrimination and coding of environmental stimuli. Color vision is based on the differential color sensitivity of retinal photoreceptors, however the developmental programs that control photoreceptor cell differentiation and specify color sensitivity are poorly understood. In Drosophila melanogaster, there is evidence that the color sensitivity of different photoreceptors in the compound eye is regulated by inductive signals between cells, but the exact nature of these signals and how they are propagated remains unknown. We conducted a genetic screen to identify additional regulators of this process and identified a novel mutation in the hibris gene. hibris encodes an irre cell recognition module protein (IRM). These immunoglobulin super family cell adhesion molecules include human neph and nephrin (NPHS1). hibris is expressed dynamically in the developing Drosophila melanogaster eye and loss-of-function mutations give rise to a diverse range of mutant phenotypes including disruption of the specification of R8 photoreceptors cell diversity. The specification of blue or green sensitivity in R8 cells is also dependent upon Notch signaling. We demonstrate that hibris is required within the retina, non-cell autonomously for these effects, suggesting an additional layer of complexity in the signaling process that produces paired expression of opsin genes in adjacent R7 and R8 photoreceptor cells.\n\nAuthor SummaryAs humans, our ability to distinguish different colors is dependent upon the presence of three different types of cone cell neurons in the retina of the eye. The cone cells express blue, green or red absorbing visual pigments that detect and discriminate between these colors. The principle of color discrimination by neurons \"tuned\" to different colors is an evolutionarily conserved specialization that occurs in many different animals. This specialization requires 1) visual pigments that detect different colors and 2) a developmental program that regulates the expression of these pigments in different types of cells. In this study we discovered that the fruit fly (Drosophila melanogaster) gene hibris is required for the developmental program that produces blue sensitive neurons in the fly retina. When we over-expressed hibris throughout the developing retina, extra blue sensitive cells were produced. These results demonstrate that if there is not enough hibris, too few blue sensitive cells form, but if there is too much hibris, too many blue sensitive cells form. Finally, we discovered that the hibris gene does not act in color sensitive neurons of the retina themselves. This surprising discovery suggests that hibris may influence development of the retina in a completely new and different way.

developmental biology