Abstract
Fragile X Syndrome is the most common form of inherited mental retardation in humans. It results from a mutation in the FMR1 gene, which encodes the translational repressor FMRP. It has been shown that overexpression of FMRP in the Drosophila eye causes a reduction in eye neuronal cell development. In this experiment, it is tested whether a similar developmental defect may result from the overexpression of FMRP in the epithelial tissue of Drosophila wings. The GAL4/UAS ectopic expression system was used to generate flies overexpressing FMRP in specific wing imaginal disc tissues. The system was driven by two different tissue-specific promoters: dpp and nub. It was found that dpp experimental wings exhibited a notch-like shape at the distal tip and a statistically significant shrunken anterior-posterior border compartment, while nub wings exhibited nearly complete shrinkage. The cause of this epithelial tissue shrinkage was explored in third instar larval stage wing discs using immunocytochemistry. The expression patterns of FMRP and activated Caspase-3, driven by dpp, were compared using fluorescence microscopy to determine whether the shrinkage may be the result of ectopic apoptosis, but no significant correlations were observed. The expression patterns of FMRP and E-cadherin were similarly compared to determine whether the shrinkage may by the result of cell structural defects, specifically defects in the formation or regulation of cell-to-cell adherens junctions. The expression patterns of these proteins were nearly identical, and the differences in their fluorescence intensities at the anterior-posterior border compared to the rest of the wing were statistically significant. These results suggest that FMRP is capable of modulating E-cadherin, and thus possibly adherens junctions. Therefore, it is concluded that overexpression of FMRP results in epithelial tissue shrinkage in the Drosophila wing, and that this shrinkage may be due to FMRP-induced E-cadherin overexpression.