The micro RNA / TET 3/ REST axis is required for olfactory globose basal cell proliferation and male behavior

In the main olfactory epithelium ( MOE ), new olfactory sensory neurons ( OSN s) are persistently generated to replace lost neurons throughout an organism's lifespan. This process predominantly depends on the proliferation of globose basal cells ( GBC s), the actively dividing stem cells in the MOE . Here, by using CRISPR /Cas9 and RNA i 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 GBC s and decreased numbers of differentiated OSN s, accompanied by abrogation of male behaviors. We further showed that in the MOE , miR‐200b/a targets the ten‐eleven translocation methylcytosine dioxygenase TET 3, which cooperates with RE 1‐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 TET 3 or REST . Our work describes a mechanism of coordination of GBC proliferation and differentiation in the MOE and olfactory male behaviors through miR‐200/ TET 3/ REST signaling.