Abstract
The murine vomeronasal organ detects pheromones, chemical signals that control or modulate many social and reproductive behaviors. Pheromone detection begins with the activation of vomeronasal receptors (VRs) expressed by vomeronasal sensory neurons (VSNs). These receptors comprise two large gene families: the V1Rs, which are expressed monogenically and monoallelically by apical VSNs, and the V2Rs, which are expressed in restricted or mutually-exclusive patterns by basal VSNs. Similar to olfactory receptor (OR) regulation in the main olfactory epithelium (MOE), VR expression involves an initial process of VR gene choice and a subsequent process of VR-driven feedback. ORs execute feedback through activation of the unfolded protein response and subsequent translation of the transcription factor Atf5. Herein, I demonstrate that Atf5 translation in the VNO requires Lsd1, an epigenetic remodeler required for OR choice. Atf5 translation is controlled by PERK-driven phosphorylation of the translation initiation factor eIF2α, indicating that activation of the unfolded protein response is required for VSN development. Finally, I show that in the VNO, Atf5 translation is widespread in mature VSNs, indicating continued PERK activation after VSN maturation. Together, these results establish points of convergence and divergence in the mechanisms underlying sensory receptor gene regulation in the two olfactory organs.