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The micro RNA / TET 3/ REST axis is required for olfactory globose basal cell proliferation and male behavior
Author(s) -
Yang Dong,
Wu Xiangbo,
Zhou Yanfen,
Wang Weina,
Wang Zhenshan
Publication year - 2020
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201949431
Subject(s) - china , library science , political science , computer science , law
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.