Background: Most animal species exhibit sexually dimorphic behaviors, many of which are linked to reproduction.\nA number of these behaviors, including blood feeding in female mosquitoes, contribute to the global spread of\nvector-borne illnesses. However, knowledge concerning the genetic basis of sexually dimorphic traits is limited in\nany organism, including mosquitoes, especially with respect to differences in the developing nervous system.\nMethods: Custom microarrays were used to examine global differences in female vs. male gene expression in the\ndeveloping pupal head of the dengue vector mosquito, Aedes aegypti. The spatial expression patterns of a subset of\ndifferentially expressed transcripts were examined in the developing female vs. male pupal brain through in situ\nhybridization experiments. Small interfering RNA (siRNA)-mediated knockdown studies were used to assess the\nputative role of Doublesex, a terminal component of the sex determination pathway, in the regulation of\nsex-specific gene expression observed in the developing pupal brain.\nResults: Transcripts (2,527), many of which were linked to proteolysis, the proteasome, metabolism, catabolic, and\nbiosynthetic processes, ion transport, cell growth, and proliferation, were found to be differentially expressed in\nA. aegypti female vs. male pupal heads. Analysis of the spatial expression patterns for a subset of dimorphically\nexpressed genes in the pupal brain validated the data set and also facilitated the identification of brain regions\nwith dimorphic gene expression. In many cases, dimorphic gene expression localized to the optic lobe. Sex-specific\ndifferences in gene expression were also detected in the antennal lobe and mushroom body. siRNA-mediated gene\ntargeting experiments demonstrated that Doublesex, a transcription factor with consensus binding sites located\nadjacent to many dimorphically expressed transcripts that function in neural development, is required for regulation\nof sex-specific gene expression in the developing A. aegypti brain.\nConclusions: These studies revealed sex-specific gene expression profiles in the developing A. aegypti pupal head and\nidentified Doublesex as a key regulator of sexually dimorphic gene expression during mosquito neural development
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