Bcl11b controls odorant receptor class choice in mice

• Published in: Communications biology Vol. 2; no. 1; p. 296
• Main Authors: Enomoto, Takayuki, Nishida, Hidefumi, Iwata, Tetsuo, Fujita, Akito, Nakayama, Kanako, Kashiwagi, Takahiro, Hatanaka, Yasue, Kondo, Hiro, Kajitani, Rei, Itoh, Takehiko, Ohmoto, Makoto, Matsumoto, Ichiro, Hirota, Junji
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 07.08.2019; Nature Publishing Group
• Subjects: 13/51; 14/32; 14/63; 38; 38/1; 38/32; 38/39; 38/61; 38/91; 42/41; 631/208/200; 631/378/2571/2578; 631/378/2624/2625; 631/378/340; 64/114; 64/60; Animals; Behavior, Animal; Biology; Biomedical and Life Sciences; Early Growth Response Protein 1 - metabolism; Female; Functional morphology; Gene Expression Regulation, Developmental; Life Sciences; Male; Mice, Inbred BALB C; Mice, Knockout; Odorants; Olfactory Bulb - metabolism; Olfactory Perception; Olfactory receptor neurons; Olfactory Receptor Neurons - metabolism; Olfactory system; Receptors, Odorant - genetics; Receptors, Odorant - metabolism; Repressor Proteins - deficiency; Repressor Proteins - genetics; Repressor Proteins - metabolism; Sensory neurons; Signal Transduction; Smell; Transcription factors; Tumor Suppressor Proteins - deficiency; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; Xenopus; Molecular neuroscience; Cell fate and cell lineage; Olfactory receptors; Gene regulation
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-019-0536-x

Each olfactory sensory neuron (OSN) expresses a single odorant receptor (OR) gene from the class I or class II repertoire in mice. The mechanisms that regulate OR class choice in OSNs remain unknown. Here, we show that the transcription factor Bcl11b determines the OR class to be expressed in OSNs. Both loss- and gain-of-function analyses demonstrate that class I is a default fate of OSNs and that Bcl11b dictates a class II OR choice by suppressing the effect of the J-element, a class I-OR enhancer. We further demonstrate that OSN-specific 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. Overall, these findings reveal a unique transcriptional mechanism mediating a binary switch for OR class choice that is crucial to both the anatomical and functional organization of the olfactory system. Enomoto et al. show that a transcription factor Bcl11b overrides a default fate of olfactory sensory neurons, class I, to dictate the class II by suppressing a class I-olfactory receptor (OR) enhancer. This study presents a transcriptional binary switch that chooses the OR class, which in turn functionally organizes the olfactory system in mice.