Goldman S A
Department of Neurology and Neuroscience, Cornell University Medical College, New York, New York 10021, USA.
J Neurobiol. 1998 Aug;36(2):267-86.
Neuronal precursor cells persist in the adult vertebrate forebrain, residing primarily in the ventricular/subventricular zone (SZ). In vivo, SZ precursors yield progeny which may die or give rise to glia. Yet they may also generate neurons, which are recruited to restricted regions such as the avian telencephalon and mammalian olfactory bulb. The survival of neurons arising from adult progenitors is dictated by both the availability of a permissive pathway for migration and the environment into which migration occurs. In the songbird higher vocal center (HVC), both humoral and contact-mediated signals modulate the migration and survival of new neurons, through an orchestrated set of hormonally regulated paracrine interactions. New neurons of the songbird brain depart the SZ to enter the brain parenchyma by migrating upon radial guide fibers, which emanate from cell bodies in the ventricular epithelium. The radial guide cells coderive with new neurons from a common progenitor, which is widespread throughout the songbird SZ. Neural precursors are also widely distributed in the adult mammalian SZ, although it is unclear whether avian and mammalian progenitor cells are homologous: Whereas neuronal recruitment persists throughout much of the songbird forebrain, in mammals it is limited to the olfactory bulb. In humans, the adult SZ appears to largely cease neurogenesis in vivo, although it, too, can produce neurons in vitro. In both rats and humans, the differentiation and survival of neurons arising from the postnatal SZ may be regulated by access to postmitotic trophic factors. Indeed, serial application of fibroblast growth factor-2 (FGF-2) and brain-derived neurotrophic factor (BDNF) has allowed the generation and maintenance of neurons from the adult human SZ. This suggests the feasibility of inducing neurogenesis in the human brain, both in situ and through implanted progenitors. In this regard, using cell-specific neural promoters coupled to fluorescent reporters, defined progenitor phenotypes may now be isolated by fluorescence-activated cell sorting. Together, these findings give hope that structural brain repair through induced neurogenesis and neurogenic implants will soon be a clinical reality.
神经元前体细胞在成年脊椎动物前脑持续存在，主要位于脑室下区（SVZ）。在体内，SVZ前体细胞产生的后代可能死亡或分化为胶质细胞。然而，它们也可能生成神经元，这些神经元会被招募到特定区域，如鸟类端脑和哺乳动物嗅球。成年祖细胞产生的神经元的存活取决于迁移许可通路的可用性以及迁移发生的环境。在鸣禽高级发声中枢（HVC）中，体液信号和接触介导信号通过一组精心编排的激素调节旁分泌相互作用，调节新神经元的迁移和存活。鸣禽大脑中的新神经元离开SVZ，通过沿着从脑室上皮细胞体发出的放射状引导纤维迁移，进入脑实质。放射状引导细胞与新神经元来源于共同的祖细胞，这种祖细胞广泛分布于鸣禽的SVZ。神经前体细胞在成年哺乳动物的SVZ中也广泛分布，不过尚不清楚鸟类和哺乳动物的祖细胞是否同源：在鸣禽的大部分前脑中，神经元的招募持续存在，而在哺乳动物中，神经元的招募仅限于嗅球。在人类中，成年SVZ在体内似乎基本停止神经发生，尽管它在体外也能产生神经元。在大鼠和人类中，出生后SVZ产生的神经元的分化和存活可能受有丝分裂后营养因子的获取调节。事实上，成纤维细胞生长因子2（FGF - 2）和脑源性神经营养因子（BDNF）的连续应用已使得从成年人类SVZ生成并维持神经元成为可能。这表明在人类大脑中诱导神经发生，无论是原位诱导还是通过植入祖细胞诱导，都是可行的。在这方面，利用与荧光报告基因偶联的细胞特异性神经启动子，现在可以通过荧光激活细胞分选分离出特定的祖细胞表型。总之，这些发现让人看到希望，即通过诱导神经发生和神经源性植入进行大脑结构修复很快将成为临床现实。
