Shared genetic requirements for ATF5 translation in the vomeronasal organ and main olfactory epithelium

• Published in: F1000 research 2018, Vol.7, p.73
• Main Author: Dalton, Ryan P
• Format: Article
• Language: English
• ISSN: 2046-1402; 2046-1402
• DOI: 10.12688/f1000research.13659.1

Background: Both 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. Methods: ATF5 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. Results: ATF5 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 eIF2a. Finally, unlike previous observations in OSNs, ATF5 was found to be widespread in the mature VNO and co-expressed with mature VSN markers. Conclusions: These 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.