13 Proneuronal Genes Drive Neurogenesis on the Road from Development to Adulthood

Elizabeth T. Buchen, S. Pleasure
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Abstract

The ongoing production of neurons in selected areas of the adult mammalian brain is tantalizing and has become an active area of research for many investigators. It is exciting to consider the functional importance of adding new neurons to mature circuits, as well as the intricate biological processes regulating their production (Meltzer et al. 2005; Ming and Song 2005; Lledo et al. 2006). Many investigators are also fascinated by the potential of repairing the injured nervous system with adult-generated neurons, those either produced in specialized adult neurogenic niches or induced in regions where little (if any) neurogenesis normally persists, such as the spinal cord or neocortex. Whether the inspiration is systems neuroscience, basic biology, or biomedical applications, the advancement of the field of neurogenesis depends on understanding the underlying molecular mechanisms regulating this process. When considering this central issue, most investigators have posited that molecular pathways important for development must have similar roles in the adult (Deisseroth et al. 2004; Meltzer et al. 2005; Ming and Song 2005). It is important to realize, however, that the number of studies demonstrating a required and specific role for any developmental regulators in adult neurogenesis is quite small. Adult neurogenesis is contingent on the functioning of the neurogenic niche, which must be produced during development, maintained during postnatal life, and regulated during adulthood. This presents a significant barrier for interpreting most genetic manipulations, as it is virtually impossible to distinguish adult requirements from developmental insults in most studies examining these pathways. To establish...
前神经元基因在发育到成年的道路上驱动神经发生
在成年哺乳动物大脑的特定区域不断产生神经元是诱人的,并已成为许多研究人员的一个活跃的研究领域。考虑到在成熟回路中添加新神经元的功能重要性,以及调节其产生的复杂生物过程,这是令人兴奋的(Meltzer等人,2005;明宋2005;Lledo et al. 2006)。许多研究人员还对用成体生成的神经元修复受损神经系统的潜力着迷,这些神经元要么产生于专门的成体神经发生龛,要么诱导于通常很少(如果有的话)神经发生的区域,如脊髓或新皮层。无论灵感来自系统神经科学、基础生物学还是生物医学应用,神经发生领域的进步取决于对调节这一过程的潜在分子机制的理解。在考虑到这一核心问题时,大多数研究人员都假设,对发育重要的分子途径在成人中也有类似的作用(deisserth et al. 2004;Meltzer等人,2005;Ming and Song 2005)。然而,重要的是要认识到,证明任何发育调节因子在成人神经发生中所必需和特定作用的研究数量相当少。成人神经发生取决于神经源性生态位的功能,它必须在发育过程中产生,在出生后生活中维持,并在成年期受到调节。这为解释大多数基因操作提出了一个重大障碍,因为在大多数检查这些途径的研究中,几乎不可能区分成人需求和发育损害。建立……
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