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Rem2 GTPase controls proliferation and apoptosis of neurons during embryo development.

机译:Rem2 GTPase在胚胎发育过程中控制神经元的增殖和凋亡。

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We 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.
机译:我们最近发现,在人类胚胎干细胞(hESC)中高表达的Rem2 GTPase维持细胞周期并控制向外胚层的适当分化,提示其在神经元发育中的作用。我们在这里描述了斑马鱼(Danio rerio)模型的使用,以确定在胚胎发生过程中Rem2的生理意义。我们显示,Rem2 RNA在斑马鱼胚胎中高度表达,直至发育2小时,随后表达降低,直到48小时,之后再次开启Rem2,直到5天。原位表达分析表明,Rem2仅在斑马鱼的大脑和眼睛的顶盖中表达。 Rem2吗啉代证明胚胎发育受损,导致神经组织丢失。我们表明,Rem2的作用机制是控制细胞凋亡和增殖,在发育的36小时达到峰值。 Rem2在hESC的一般分化条件下被下调,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Rem2通过调节增殖和凋亡在胚胎发生过程中对神经元发育至关重要。我们提出了一个模型,其中Rem2 GTPase是在胚胎发生的早期阶段以及在以后的胚胎发育过程中神经元存活期间维持多能性的关键调节因子。

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