Karus Michael, Blaess Sandra, Brüstle Oliver
Institute of Reconstructive Neurobiology, University of Bonn LIFE&BRAIN Center, and LIFE&BRAIN GmbH, 53127, Bonn, Germany.
J Comp Neurol. 2014 Aug 15;522(12):2831-44. doi: 10.1002/cne.23608. Epub 2014 May 7.
Despite being a subject of intensive research, the mechanisms underlying the formation of neural tissue architectures during development of the central nervous system remain largely enigmatic. So far, studies into neural pattern formation have been restricted mainly to animal experiments. With the advent of pluripotent stem cells it has become possible to explore early steps of nervous system development in vitro. These studies have unraveled a remarkable propensity of primitive neural cells to self-organize into primitive patterns such as neural tube-like rosettes in vitro. Data from more advanced 3D culture systems indicate that this intrinsic propensity for self-organization can even extend to the formation of complex architectures such as a multilayered cortical neuroepithelium or an entire optic cup. These novel experimental paradigms not only demonstrate the enormous self-organization capacity of neural stem cells, they also provide exciting prospects for studying the earliest steps of human neural tissue development and the pathogenesis of brain malformations in reductionist in vitro paradigms.
尽管中枢神经系统发育过程中神经组织结构形成的潜在机制一直是深入研究的课题,但在很大程度上仍然是个谜。到目前为止,对神经模式形成的研究主要局限于动物实验。随着多能干细胞的出现,在体外探索神经系统发育的早期步骤已成为可能。这些研究揭示了原始神经细胞在体外自组织成原始模式(如神经管样玫瑰花结)的显著倾向。来自更先进的3D培养系统的数据表明,这种内在的自组织倾向甚至可以扩展到形成复杂结构,如多层皮质神经上皮或整个视杯。这些新的实验范式不仅证明了神经干细胞巨大的自组织能力,也为在简化的体外范式中研究人类神经组织发育的最早步骤和脑畸形的发病机制提供了令人兴奋的前景。