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000169864 0247_ $$2doi$$adoi: 10.1002/stem.3435
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000169864 0247_ $$2doi$$a10.1002/stem.3435
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000169864 041__ $$aEnglish
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000169864 1001_ $$aWang, Yu$$b0
000169864 245__ $$aImpaired generation of mature neurons due to extended expression of Tlx by repressing Sox2 transcriptional activity.
000169864 260__ $$aHoboken, NJ$$bWiley-Blackwell$$c2021
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000169864 500__ $$aNeuerburg, Bock: Division of Molecular Biology of the Cell I, German Cancer Research Center (DKFZ) /2021 Nov;39(11):1520-1531 /DKFZ-ZMBH Alliance
000169864 520__ $$aAs a master regulator of the dynamic process of adult neurogenesis, timely expression and regulation of the orphan nuclear receptor Tailless (Tlx) is essential. However, there is no study yet to directly investigate the essential role of precise spatiotemporal expressed Tlx. Here, we generated a conditional gain of Tlx expression transgenic mouse model, which allowed the extended Tlx expression in neural stem cells (NSCs) and their progeny by mating with a TlxCreERT2 mouse line. We demonstrate that extended expression of Tlx induced the impaired generation of mature neurons in adult subventricular zone and subgranular zone. Furthermore, we elucidated for the first time that this mutation decreased the endogenous expression of Sox2 by directly binding to its promoter. Restoration experiments further confirmed that Sox2 partially rescued these neuron maturation defects. Together, these findings not only highlight the importance of shutting-off Tlx on time in controlling NSC behavior, but also provide insights for further understanding adult neurogenesis and developing treatment strategies for neurological disorders.
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000169864 650_7 $$2Other$$aSox2
000169864 650_7 $$2Other$$aTlx
000169864 650_7 $$2Other$$aadult neurogenesis
000169864 650_7 $$2Other$$aneural differentiation
000169864 650_7 $$2Other$$aneural stem cell
000169864 7001_ $$aLi, Bin$$b1
000169864 7001_ $$aDong, Lianwei$$b2
000169864 7001_ $$aDuan, Weibing$$b3
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000169864 7001_ $$aZhang, Han$$b5
000169864 7001_ $$aJiang, Xijuan$$b6
000169864 7001_ $$aShao, Rui$$b7
000169864 7001_ $$aZhu, Yan$$b8
000169864 7001_ $$0P:(DE-He78)5caa069445d78479a7ceae926328e5d8$$aBock, Dagmar$$b9$$udkfz
000169864 7001_ $$aLiu, Erwei$$b10
000169864 7001_ $$aWang, Hong$$b11
000169864 7001_ $$aZhang, Yunsha$$b12
000169864 7001_ $$aDai, Yifan$$b13
000169864 7001_ $$aYang, Haiyuan$$b14
000169864 7001_ $$00000-0001-5129-4449$$aWang, Ying$$b15
000169864 773__ $$0PERI:(DE-600)2030643-X$$a10.1002/stem.3435$$n11$$p1520-1531$$tStem cells$$v39$$x1066-5099$$y2021
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000169864 9141_ $$y2021
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