2-B-S37-3 榎本 孝幸¹、岩田 哲郎¹、西田 秀史¹、梶谷 嶺¹、伊藤 武彦¹、應本 真²、松本 一朗²、〇廣田 順二¹ Enomoto Takayuki¹, Iwata Tetsuo¹, Nishida Hidefumi¹, Kajitani Rei¹, Itoh Takehiko¹, Ohmoto Makoto², Matsumoto Ichiro², Hirota Junji^{1 1}東京工業大学・生命理工学院、²モネル化学感覚研究所 ¹Tokyo Institute of Technology, Life Science and Technology, ²Monell Chemical Senses Center In the quarter-century since odorant receptor (OR) genes were first identified, considerable effort has gone into understanding how each OSN chooses to express a single receptor gene. In order to make this choice possible, OSNs must first choose between two classes of OR genes, class I and class II ORs, a fundamental distinction that is critical to both the anatomical and functional organization of olfactory system. However, the mechanisms that regulate the OR class choice have remained unknown. In this paper, we identify the transcription factor Bcl11b as a critical regulator that determines the OR class to be expressed in OSNs. Both loss- and gain-of-function mutations of Bcl11b demonstrate that class I is a default class of OR to be expressed in OSNs and that Bcl11b dictates the class II OR choice by suppressing the J element, a class I OR enhancer. We further demonstrate that genetic manipulations of Bcl11b bias the OR class choice, generating mice with "class I-dominant" and "class II-dominant" noses, which display contrasting innate olfactory behaviors to two distinct aversive odorants, indicating that alternations of the OR class choice in peripheral OSNs change the odor world for mice. Overall, these findings reveal a unique transcriptional mechanism that serves as a binary switch for OR class choice that is crucial to both the anatomical and functional organization of the olfactory system.