Rem2 GTPase controls proliferation and apoptosis of neurons during embryo development
Rem2 GTPase controls proliferation and apoptosis of neurons during embryo development
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DOI：
10.4161/cc.9.17.12719
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发表时间：
2010-09-01
期刊：
影响因子：
4.3
通讯作者：
Izpisua Belmonte, Juan Carlos
中科院分区：
文献类型：
--
作者：
Edel, Michael J.;Boue, Stephanie;Izpisua Belmonte, Juan Carlos
我们最近发现Rem 2 GT3在人胚胎干细胞（hESC）中高度表达，维持细胞周期并控制向外胚层的适当分化，表明在神经元发育中的作用。我们在这里描述的斑马鱼（Danio rerio）模型，以确定在胚胎发育过程中的Rem 2的生理意义。我们发现，Rem 2 RNA在斑马鱼胚胎中高度表达长达2小时的发育，随后表达减少，直到48小时，之后Rem 2再次开启，直到5天。原位表达分析表明，Rem 2只在斑马鱼的大脑和眼睛的顶盖中表达。Rem 2吗啉代显示胚胎发育受损，导致神经组织损失。我们发现Rem 2的作用机制是控制细胞凋亡和增殖，在发育36小时达到峰值。Rem 2在hESC的一般分化条件下下调，并且在大多数分化细胞中表达较低;然而，它随着神经元发育而上调。这表明Rem 2通过调节增殖和凋亡对胚胎发生期间的神经元发育至关重要。我们提出了一个模型，其中Rem 2 GTdR是一个关键的调节器，在胚胎发育的早期阶段维持多能性和在胚胎发育后期的神经元的存活。
W e have recently found that Rem2 GTPase, highly expressed in human embryonic stem cells (hESC), maintains the cell cycle and controls proper differentiation towards ectoderm, suggesting a role in neuronal development. We describe here the use of the zebrafish (Danio rerio) model to determine the physiological significance of Rem2 during embryogenesis. We show that Rem2 RNA is highly expressed in zebrafish embryos up to 2 hours of development followed by a decrease in expression until 48 hours when afterwards Rem2 is switched on again until 5 days. In situ expression analysis reveals that Rem2 is expressed exclusively in the tectum of the brain and eye of the zebrafish. Rem2 morpholino demonstrates impaired embryo development resulting in loss of neural tissue. We show that the mechanism of action of Rem2 is to control apoptosis and proliferation, peaking at 36 hours of development. Rem2 is down-regulated under general differentiation conditions of hESC and is lower expressed in most differentiated cells; however, it is upregulated with neuronal development. This suggests that Rem2 is critical for neuronal development during embryogenesis by regulating proliferation and apoptosis. We propose a model in which Rem2 GTPase is a key regulator maintaining pluripotency during early stages of embryogenesis and survival of neurons during later embryonic development.