Interaction between Oc-1 and Lmx1a promotes ventral midbrain dopamine neural stem cells differentiation into dopamine neurons

Interaction between Oc-1 and Lmx1a promotes ventral midbrain dopamine neural stem cells differentiation into dopamine neurons
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Oc-1和Lmx1a之间的相互作用促进腹侧中脑多巴胺神经干细胞分化为多巴胺神经元

DOI:
10.1016/j.brainres.2015.02.046
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发表时间:
2015-05
期刊:
影响因子:
2.9
通讯作者:
Chen, Dong-Bo
Chen, Dong-Bo
中科院分区:
医学3区
文献类型:
--
作者:
Lei, Zhi-nian;Wang, Xi;Deng, Yong-Jian;Chen, Dong-Bo

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最近的研究表明Onecut(Oc)转录因子可能参与中脑多巴胺能神经元(mdDA)的早期发育。Oc因子的表达谱与Lmx 1a的表达谱相匹配,Lmx 1a是mDA神经元发育中的重要内在转录因子。此外,Wnt 1-Lmx 1a通路控制mdDA分化。然而,它们的表达动力学和分子机制仍有待确定。为了解决这些问题,我们假设Oc-1和Lmx 1a之间的串扰通过经典的Wnt-β-catenin途径调节mdDA的特化和分化。我们发现Oc-1和Lmx 1a在胚胎至成人腹侧中脑(VM)组织中显示出非常相似的表达谱。Oc-1可调节腹侧中脑神经干细胞(vmNSCs)的增殖和分化。Oc-1的下调降低了Lmx 1a的转录和蛋白水平。Oc-1与lmx 1a在体外VMNSCs和体内VM组织中相互作用。敲低Lmx 1a可降低vmNSCs中Oc-1和Wnt 1的表达。在vmNSC中抑制Wnt 1信号传导引起类似的反应。提示Oc-1通过Wnt 1-Lmx 1a通路与Lmx 1a相互作用,促进VMNSCs向多巴胺神经元分化。
Recent studies have shown that Onecut (Oc) transcription factors may be involved in the early development of midbrain dopaminergic neurons (mdDA). The expression profile of Oc factors matches that of Lmx1a, an important intrinsic transcription factor in the development of mDA neuron. Moreover, the Wnt1-Lmx1a pathway controls the mdDA differentiation. However, their expression dynamics and molecular mechanisms remain to be determined. To address these issues, we hypothesize that cross-talk between Oc-1 and Lmx1a regulates the mdDA specification and differentiation through the canonical Wnt-β-catenin pathway. We found that Oc-1 and Lmx1a displayed a very similar expression profile from embryonic to adult ventral midbrain (VM) tissues. Oc-1 regulated the proliferation and differentiation of ventral midbrain neural stem cells (vmNSCs). Downregulation of Oc-1 decreased both transcript and protein level of Lmx1a. Oc-1 interacted with lmx1a in vmNSCs in vitro and in VM tissues in vivo. Knockdown of Lmx1a reduced the expression of Oc-1 and Wnt1 in vmNSCs. Inhibiting Wnt1 signaling in vmNSCs provoked similar responses. Our data suggested that Oc-1 interacts with Lmx1a to promote vmNSCs differentiation into dopamine neuron through Wnt1-Lmx1a pathway.
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