In the main olfactory epithelium (MOE), new olfactory sensory neurons (OSNs) are persistently generated to replace lost neurons throughout an organism's lifespan. This process predominantly depends on the proliferation of globose basal cells (GBCs), the actively dividing stem cells in the MOE. Here, by using CRISPR/Cas9 and RNAi coupled with adeno‐associated virus (AAV) nose delivery approaches, we demonstrated that knockdown of miR‐200b/a in the MOE resulted in supernumerary Mash1‐marked GBCs and decreased numbers of differentiated OSNs, accompanied by abrogation of male behaviors. We further showed that in the MOE, miR‐200b/a targets the ten‐eleven translocation methylcytosine dioxygenase TET3, which cooperates with RE1‐silencing transcription factor (REST) to exert their functions. Deficiencies including proliferation, differentiation, and behaviors illustrated in miR‐200b/a knockdown mice were rescued by suppressing either TET3 or REST. Our work describes a mechanism of coordination of GBC proliferation and differentiation in the MOE and olfactory male behaviors through miR‐200/TET3/REST signaling.

中文翻译：

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microRNA/TET3/REST 轴是嗅球状基底细胞增殖和男性行为所必需的。

在主嗅觉上皮 (MOE) 中，新的嗅觉感觉神经元 (OSN) 不断生成，以取代生物体整个生命周期中丢失的神经元。这个过程主要取决于球状基底细胞 (GBC) 的增殖，这是 MOE 中积极分裂的干细胞。在这里，通过使用 CRISPR/Cas9 和 RNAi 结合腺相关病毒 (AAV) 鼻递送方法，我们证明了 MOE 中 miR-200b/a 的敲低导致多余的 Mash1 标记的 GBC 和分化的 OSN 数量减少，伴随着通过废除男性行为。我们进一步表明，在 MOE 中，miR-200b/a 靶向 10-11 易位甲基胞嘧啶双加氧酶 TET3，它与 RE1 沉默转录因子 (REST) 合作发挥其功能。缺陷包括增殖、分化、miR-200b/a 敲低小鼠的行为通过抑制 TET3 或 REST 得以挽救。我们的工作描述了通过 miR-200/TET3/REST 信号传导在 MOE 和嗅觉男性行为中协调 GBC 增殖和分化的机制。