Shared Genetic Requirements for Atf5 Translation in the Vomeronasal Organ and Main Olfactory Epithelium

Abstract

BackgroundBoth olfactory sensory neurons (OSNs) and vomeronasal sensory neurons (VSNs) require the transcription factor Atf5 for maturation and survival. In OSNs, ATF5 translation is controlled by olfactory receptor (OR) expression-mediated activation of the PERK branch of the unfolded protein response. This study evaluated whether OSNs and VSNs share genetic requirements for ATF5 translation.\n\nMethodsATF5 immunoreactivity was assayed in whole vomeronasal organs from a series of genetic mutant animals identified in studies of OR gene choice, OR feedback, and regulation and OSN development.\n\nResultsATF5 expression in VSNs required the histone demethylase Lsd1, which has been previously reported to be required for OR expression. ATF5 expression also required PERK-mediated phosphorylation of the translation initiation factor eIF2. Finally, unlike previous observations in OSNs, ATF5 was found to be widespread in the mature VNO and co-expressed with mature VSN markers.\n\nConclusionsThese data suggest that the initiation of ATF5 translation in VSNs and OSNs is under similar regulation, and that persistent/prolonged ATF5 translation in VSNs may serve VSN-specific gene regulatory programs. This study firmly establishes the unfolded protein response as a major controller of sensory neuronal maturation and diversification.