Zfhx3 is required for the differentiation of late born D1-type medium spiny neurons

Zfhx3 is required for the differentiation of late born D1-type medium spiny neurons
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Zfhx3 是晚生 D1 型中型多棘神经元分化所必需的

DOI:
10.1016/j.expneurol.2019.113055
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发表时间:
2019-09
影响因子:
5.3
通讯作者:
Yang Zhengang
Yang Zhengang
中科院分区:
医学2区
文献类型:
--
作者:
Zhang Zhuangzhi;Wei Song;Du Heng;Su Zihao;Wen Yan;Shang Zicong;Song Xiaolei;Xu Zhejun;You Yan;Yang Zhengang

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纹状体是基底神经节的主要组成部分,由尾壳核、丘脑核和嗅结节组成。纹状体主要投射神经元由具有两种多巴胺受体的中型多刺神经元(MSN)组成:DRD 1(D1 MSN)和DRD 2(D2 MSN)。在本研究中,我们证明,Zfhx 3是强烈表达在脑室下区(SVZ)/外套带(MZ)的边界的外侧神经节隆起(LGE),其表达在纹状体下调,在出生后的第一周。在细胞水平,Zfhx 3选择性地在未成熟的D1 MSN中表达。在Zfhx 3条件性基因敲除中,我们观察到在E16.5和P0的LGE SVZ中祖细胞的积累,以及出生后纹状体中凋亡的增加。BrdU出生测定实验表明,晚出生的D1 MSN生产受到损害。因此,我们观察到在纹状体中的Zfhx 3条件性敲除在P11时D1 MSNs的数量显著减少,而D2 MSNs的数量保持不受影响。我们的结论是Zfhx 3在晚出生的D1 MSNs的分化和存活中起着关键作用。
The striatum, the major component of the basal ganglia, consists of the caudate-putamen, nucleus accumbens and olfactory tubercle. The striatal principal projection neurons are comprised of medium spiny neurons (MSNs) with two dopamine receptors: DRD1 (D1 MSNs) and DRD2 (D2 MSNs). In the present study, we demonstrate thatZfhx3is strongly expressed in the boundary of the subventricular zone (SVZ)/mantle zone (MZ) of the lateral ganglionic eminence (LGE), and its expression in the striatum is downregulated during the first postnatal week. At the cellular level,Zfhx3is selectively expressed in immature D1 MSNs. InZfhx3conditional knockouts, we observed an accumulation of progenitors in the LGE SVZ at E16.5 and P0, and an increase in apoptosis in the postnatal striatum. BrdU birthdating experiments revealed that late born D1 MSN production was compromised. Accordingly, we observed a significant reduction in the number of D1 MSNs, whereas the number of D2 MSNs remained unaffected in the striatum ofZfhx3conditional knockouts at P11. We concluded thatZfhx3plays a critical role in the differentiation and survival of late born D1 MSNs.
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