Faigle Roland, Song Hongjun
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Biochim Biophys Acta. 2013 Feb;1830(2):2435-48. doi: 10.1016/j.bbagen.2012.09.002. Epub 2012 Sep 12.
Adult neurogenesis occurs throughout life in discrete regions of the mammalian brain and is tightly regulated via both extrinsic environmental influences and intrinsic genetic factors. In recent years, several crucial signaling pathways have been identified in regulating self-renewal, proliferation, and differentiation of neural stem cells, as well as migration and functional integration of developing neurons in the adult brain.
Here we review our current understanding of signaling mechanisms, including Wnt, notch, sonic hedgehog, growth and neurotrophic factors, bone morphogenetic proteins, neurotransmitters, transcription factors, and epigenetic modulators, and crosstalk between these signaling pathways in the regulation of adult neurogenesis. We also highlight emerging principles in the vastly growing field of adult neural stem cell biology and neural plasticity.
Recent methodological advances have enabled the field to identify signaling mechanisms that fine-tune and coordinate neurogenesis in the adult brain, leading to a better characterization of both cell-intrinsic and environmental cues defining the neurogenic niche. Significant questions related to niche cell identity and underlying regulatory mechanisms remain to be fully addressed and will be the focus of future studies.
A full understanding of the role and function of individual signaling pathways in regulating neural stem cells and generation and integration of newborn neurons in the adult brain may lead to targeted new therapies for neurological diseases in humans. This article is part of a Special Issue entitled Biochemistry of Stem Cells.
成年神经发生在哺乳动物大脑的离散区域终生存在，并通过外在环境影响和内在遗传因素受到严格调控。近年来，在调节神经干细胞的自我更新、增殖和分化，以及成年大脑中发育神经元的迁移和功能整合方面，已经确定了几种关键的信号通路。
在此，我们综述了我们目前对信号机制的理解，包括Wnt、Notch、音猬因子、生长和神经营养因子、骨形态发生蛋白、神经递质、转录因子和表观遗传调节剂，以及这些信号通路在调节成年神经发生中的相互作用。我们还强调了成年神经干细胞生物学和神经可塑性这一快速发展领域中的新兴原则。
最近的方法学进展使该领域能够识别在成年大脑中微调并协调神经发生的信号机制，从而更好地表征定义神经源性微环境的细胞内在和环境线索。与微环境细胞身份和潜在调控机制相关的重大问题仍有待充分解决，将成为未来研究的重点。
全面了解各个信号通路在调节神经干细胞以及成年大脑中新生神经元的生成和整合中的作用和功能，可能会带来针对人类神经疾病的靶向新疗法。本文是名为“干细胞生物化学”的特刊的一部分。
