SOX2 Regulates Neuronal Differentiation of the Suprachiasmatic Nucleus.
SOX2 Regulates Neuronal Differentiation of the Suprachiasmatic Nucleus.
复制标题
DOI：
10.3390/ijms23010229
复制
发表时间：
2021-12-26
影响因子：
5.6
通讯作者：
Cheng HM
中科院分区：
文献类型：
--
作者：
Cheng AH;Fung SW;Hegazi S;Abdalla OHMH;Cheng HM
在哺乳动物中，下丘脑视交叉上核(SCN)作为中央昼夜节律的起搏器，根据环境的明/暗周期来协调行为和生理节奏。构成SCN的神经元在解剖学和功能上是不同的，但尽管它们具有重要的生理意义，但人们对引导它们具体化和分化的途径知之甚少。在此，我们报道了胚胎SCN中需要干细胞/祖细胞转录因子性别决定区Y-box 2(SOX2)来控制富含SCN的神经肽和转录因子的表达。在发育中的SCN中，去除Sox2会导致胚胎15.5天时昼夜节律神经肽的下调，随后参与SCN发育的两个转录因子Lhx1和Six6的表达减少。胸腺嘧啶核苷类似物滞留实验显示，SOX2缺乏导致出生后SCN神经元在细胞清除期间存活率降低，但不影响祖细胞的增殖或SCN的特性。我们的结果证实SOX2是发育中的SCN内神经元正常分化和存活所必需的转录因子。
In mammals, the hypothalamic suprachiasmatic nucleus (SCN) functions as the central circadian pacemaker, orchestrating behavioral and physiological rhythms in alignment to the environmental light/dark cycle. The neurons that comprise the SCN are anatomically and functionally heterogeneous, but despite their physiological importance, little is known about the pathways that guide their specification and differentiation. Here, we report that the stem/progenitor cell transcription factor, Sex determining region Y-box 2 (Sox2), is required in the embryonic SCN to control the expression of SCN-enriched neuropeptides and transcription factors. Ablation of Sox2 in the developing SCN leads to downregulation of circadian neuropeptides as early as embryonic day (E) 15.5, followed by a decrease in the expression of two transcription factors involved in SCN development, Lhx1 and Six6, in neonates. Thymidine analog-retention assays revealed that Sox2 deficiency contributed to reduced survival of SCN neurons during the postnatal period of cell clearance, but did not affect progenitor cell proliferation or SCN specification. Our results identify SOX2 as an essential transcription factor for the proper differentiation and survival of neurons within the developing SCN.
登录
查看更多内容
影响因子：
64.8
作者：
Cheng, MY;Bullock, CM;Zhou, QY
通讯作者：
Zhou, QY
影响因子：
4.6
作者：
Cavallaro, Maurizio;Mariani, Jessica;Nicolis, Silvia K.
通讯作者：
Nicolis, Silvia K.
影响因子：
2.5
作者：
Ahern, Todd H.;Krug, Stefanie;Forger, Nancy G.
通讯作者：
Forger, Nancy G.
影响因子：
3.5
作者：
Clark, Daniel D.;Gorman, Michael R.;Mellon, Pamela L.
通讯作者：
Mellon, Pamela L.
影响因子：
23.9
作者：
Gascon, Sergio;Murenu, Elisa;Goetz, Magdalena
通讯作者：
Goetz, Magdalena