Urbán Noelia, Guillemot François
Department of Molecular Neurobiology, MRC National Institute for Medical Research London, UK.
Front Cell Neurosci. 2014 Nov 27;8:396. doi: 10.3389/fncel.2014.00396. eCollection 2014.
Neurogenesis persists in adult mammals in specific brain areas, known as neurogenic niches. Adult neurogenesis is highly dynamic and is modulated by multiple physiological stimuli and pathological states. There is a strong interest in understanding how this process is regulated, particularly since active neuronal production has been demonstrated in both the hippocampus and the subventricular zone (SVZ) of adult humans. The molecular mechanisms that control neurogenesis have been extensively studied during embryonic development. Therefore, we have a broad knowledge of the intrinsic factors and extracellular signaling pathways driving proliferation and differentiation of embryonic neural precursors. Many of these factors also play important roles during adult neurogenesis, but essential differences exist in the biological responses of neural precursors in the embryonic and adult contexts. Because adult neural stem cells (NSCs) are normally found in a quiescent state, regulatory pathways can affect adult neurogenesis in ways that have no clear counterpart during embryogenesis. BMP signaling, for instance, regulates NSC behavior both during embryonic and adult neurogenesis. However, this pathway maintains stem cell proliferation in the embryo, while it promotes quiescence to prevent stem cell exhaustion in the adult brain. In this review, we will compare and contrast the functions of transcription factors (TFs) and other regulatory molecules in the embryonic brain and in adult neurogenic regions of the adult brain in the mouse, with a special focus on the hippocampal niche and on the regulation of the balance between quiescence and activation of adult NSCs in this region.
神经发生在成年哺乳动物的特定脑区持续存在,这些脑区被称为神经发生微环境。成年神经发生具有高度动态性,并受到多种生理刺激和病理状态的调节。人们对了解这一过程如何被调控有着浓厚的兴趣,特别是因为在成年人类的海马体和脑室下区(SVZ)都已证实存在活跃的神经元生成。在胚胎发育过程中,控制神经发生的分子机制已得到广泛研究。因此,我们对驱动胚胎神经前体细胞增殖和分化的内在因素及细胞外信号通路有广泛的了解。其中许多因素在成年神经发生过程中也发挥着重要作用,但胚胎期和成年期神经前体细胞的生物学反应存在本质差异。由于成年神经干细胞(NSCs)通常处于静止状态,调控通路对成年神经发生的影响方式在胚胎发育过程中并无明显对应。例如,骨形态发生蛋白(BMP)信号通路在胚胎期和成年期神经发生过程中均调节神经干细胞的行为。然而,该通路在胚胎中维持干细胞增殖,而在成年大脑中则促进静止状态以防止干细胞耗竭。在本综述中,我们将比较和对比转录因子(TFs)及其他调控分子在小鼠胚胎脑和成年脑成年神经发生区域中的功能,特别关注海马体微环境以及该区域成年神经干细胞静止与激活平衡的调控。