The Dysregulation of Tuning Receptors and Transcription Factors in the Antennae of Orco and Ir8a Mutants in Aedes aegypti Suggests a Chemoreceptor Regulatory Mechanism Involving the MMB/dREAM Complex

Olfaction has been extensively studied in the yellow fever mosquito, <i>Aedes aegypti</i>. This species uses its sense of smell to find blood hosts and other resources, contributing to its impact as a vector for human pathogens. Two major families of protein-coding genes, the odorant receptors (<i>Ors</i>) and the ionotropic receptors (<i>Irs</i>), provide the mosquito with sensitivities to distinct classes of volatile compounds in the antennae. Individual tuning receptors in both families require co-receptors for functionality: <i>Orco</i> for all <i>Ors</i>, and <i>Ir8a</i> for many <i>Irs</i>, especially ones that are involved in carboxylic acid detection. In <i>Drosophila melanogaster</i>, disruptions of <i>Orco</i> or <i>Ir8a</i> impair receptor function, tuning receptor expression, and membrane localization, leading to general anosmia. We reasoned that <i>Orco</i> and <i>Ir8a</i> might also be important for coordinated chemosensory receptor expression in the antennal sensory neurons of <i>Ae. aegypti</i>. To test this, we performed RNAseq and differential expression analysis in wildtype versus <i>Orco</i>^-/- and <i>Ir8a</i>^-/- mutant adult female antennae. Our analyses revealed <i>Or</i> and <i>Ir</i> tuning receptors are broadly under-expressed in <i>Orco</i>^-/- mutants, while a subset of tuning <i>Irs</i> are under-expressed in <i>Ir8a</i> mutants. Other chemosensory and non-chemosensory genes are also dysregulated in these mutants. Furthermore, we identify differentially expressed transcription factors including homologs of the <i>Drosophila melanogaster Mip120</i> gene. These data suggest a previously unknown pleiotropic role for the <i>Orco</i> and <i>Ir8a</i> co-receptors in the coordination of expression of chemosensory receptors within the antennae of <i>Ae. aegypti</i> by participating in a feedback loop involving <i>amos</i> and members of the <i>MMB/dREAM</i> complex.