Costa Marcos Romualdo, Götz Magdalena, Berninger Benedikt
Edmond and Lily Safra International Institute of Neuroscience of Natal, 59066-060 Natal, Brazil.
Brain Res Rev. 2010 May;63(1-2):47-59. doi: 10.1016/j.brainresrev.2010.01.002. Epub 2010 Jan 21.
One of the most intriguing discoveries during the last decade of developmental neurobiology is the fact that both in the developing and adult nervous system neural stem cells often turn out to have a glial identity: Radial glia generates neurons in the developing telencephalon of fish, birds and mammals and astro/radial glial stem cells in specialized neurogenic zones give rise to new neurons throughout life. What are the extrinsic signals acting on and the intrinsic signals acting within these glial populations endowing these with a neurogenic potential, whilst most other glia seemingly lack it? Studies on postnatal astroglia shed interesting light on this question as they are the intermediate between neurogenic radial glia and mature parenchymal astrocytes. At least in vitro their decision to acquire a glial fate is not yet irrevocable as forced expression of a single neurogenic transcription factor enables them to transgress their lineage and to give rise to fully functional neurons acquiring specific subtype characteristics. But even bona fide non-neurogenic glia in the adult nervous system can regain some of their radial glial heritage following injury as exemplified by reactive astroglia in the cerebral cortex and Müller glia in the retina. In this review first we will follow the direction of the physiological times' arrow, along which radial glia become transformed on one side into mature astrocytes gradually losing their neurogenic potential, while some of them seem to escape this dire destiny to settle in the few neurogenic oases of the adult brain where they generate neurons and glia throughout life. But we will also see how pathophysiological conditions partially can reverse the arrow of time reactivating the parenchymal astroglia to re-acquire some of the hallmarks of neural stem cells or progenitors. We will close this review with some thoughts on the surprising compatibility of the co-existence of a neural stem cell and glial identity within the very same cell from the perspective of the concept of transcriptional core networks.
发育神经生物学过去十年间最引人入胜的发现之一是，在发育中的和成年的神经系统中，神经干细胞常常被证明具有神经胶质细胞的特性：放射状胶质细胞在鱼类、鸟类和哺乳动物发育中的端脑中产生神经元，而在特殊神经发生区域的星形/放射状胶质干细胞在整个生命过程中产生新的神经元。作用于这些神经胶质细胞群体的外在信号以及在这些群体内部起作用的内在信号是什么，赋予了它们神经发生的潜能，而大多数其他神经胶质细胞似乎却缺乏这种潜能呢？对出生后星形胶质细胞的研究为这个问题提供了有趣的线索，因为它们是神经发生的放射状胶质细胞和成熟实质星形胶质细胞之间的中间状态。至少在体外，它们决定获得神经胶质细胞命运的过程并非不可逆转，因为单一神经发生转录因子的强制表达能使它们跨越其谱系，产生具有特定亚型特征的功能完全正常的神经元。但即使是成年神经系统中真正的非神经发生性神经胶质细胞，在受伤后也能恢复其部分放射状胶质细胞的特性，如大脑皮质中的反应性星形胶质细胞和视网膜中的穆勒胶质细胞就是例证。在这篇综述中，首先我们将顺着生理时间之箭的方向，沿着这条路径，放射状胶质细胞一方面逐渐转变为成熟星形胶质细胞，逐渐失去其神经发生潜能，而其中一些细胞似乎逃脱了这种可怕的命运，定居在成人大脑中少数神经发生的“绿洲”中，在那里它们终生产生神经元和神经胶质细胞。但我们也将看到病理生理状况如何能部分逆转时间之箭，重新激活实质星形胶质细胞，使其重新获得神经干细胞或祖细胞的一些特征。我们将从转录核心网络概念的角度，对神经干细胞和神经胶质细胞特性在同一细胞中共存的惊人兼容性进行一些思考，以此结束本综述。
