Briscoe James, Novitch Bennett G
Developmental Neurobiology, National Institute for Medical Research, Mill Hill, London NW7 1AA, UK.
Philos Trans R Soc Lond B Biol Sci. 2008 Jan 12;363(1489):57-70. doi: 10.1098/rstb.2006.2012.
The assembly of neural circuits in the vertebrate central nervous system depends on the organized generation of specific neuronal subtypes. Studies over recent years have begun to reveal the principles and elucidate some of the detailed mechanisms that underlie these processes. In general, exposure to different types and concentrations of signals directs neural progenitor populations to generate specific subtypes of neurons. These signals function by regulating the expression of intrinsic determinants, notably transcription factors, which specify the fate of cells as they differentiate into neurons. In this review, we illustrate these concepts by focusing on the generation of neurons in ventral regions of the spinal cord, where detailed knowledge of the mechanisms that regulate cell identity has provided insight into the development of a number of neuronal subtypes, including motor neurons. A greater knowledge of the molecular control of neural development is likely to have practical benefits in understanding the causes and consequences of neurological diseases. Moreover, recent studies have demonstrated how an understanding of normal neural development can be applied to direct differentiation of stem cells in vitro to specific neuronal subtypes. This type of rational manipulation of stem cells may represent the first step in the development of treatments based on therapeutic replacement of diseased or damaged nervous tissue.
脊椎动物中枢神经系统中神经回路的组装依赖于特定神经元亚型的有序生成。近年来的研究已开始揭示这些过程背后的原理并阐明一些详细机制。一般来说,暴露于不同类型和浓度的信号会引导神经祖细胞群体生成特定的神经元亚型。这些信号通过调节内在决定因素(特别是转录因子)的表达来发挥作用,这些转录因子在细胞分化为神经元时决定细胞的命运。在本综述中,我们通过聚焦脊髓腹侧区域神经元的生成来说明这些概念,在该区域,对调节细胞身份机制的详细了解为包括运动神经元在内的多种神经元亚型的发育提供了见解。对神经发育分子控制的更深入了解可能在理解神经疾病的病因和后果方面具有实际益处。此外,最近的研究已经证明,对正常神经发育的理解如何应用于体外将干细胞定向分化为特定的神经元亚型。这种对干细胞的合理操作可能代表了基于治疗性替换患病或受损神经组织的治疗方法开发的第一步。