Bcl11b controls odorant receptor class choice in mice
Bcl11b controls odorant receptor class choice in mice
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DOI：
10.1038/s42003-019-0536-x
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发表时间：
2019-08-07
影响因子：
5.9
通讯作者：
Hirota, Junji
中科院分区：
文献类型：
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作者：
Enomoto, Takayuki;Nishida, Hidefumi;Hirota, Junji
每个嗅觉感觉神经元（OSN）表达一个单一的气味受体（OR）基因，这些基因来自小鼠的I类或II类库。在osn中调控OR类选择的机制尚不清楚。在这里，我们发现转录因子Bcl11b决定了osn中表达的OR类。功能损失和功能增益分析都表明，I类是osn的默认命运，Bcl11b通过抑制I类OR增强子j元素的作用来决定II类OR选择。我们进一步证明，osn特异性的Bcl11b基因操作偏向于OR类选择，产生具有“i类优势”和“ii类优势”鼻子的小鼠，它们对两种不同的厌恶气味表现出截然不同的先天嗅觉行为。总的来说，这些发现揭示了一种独特的转录机制，介导了嗅觉系统解剖和功能组织中OR类选择的二元切换。
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.