Lim Daniel A, Alvarez-Buylla Arturo
Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF, Department of Neurological Surgery, University of California, San Francisco, California 94143.
Cold Spring Harb Perspect Biol. 2016 May 2;8(5):a018820. doi: 10.1101/cshperspect.a018820.
A large population of neural stem/precursor cells (NSCs) persists in the ventricular-subventricular zone (V-SVZ) located in the walls of the lateral brain ventricles. V-SVZ NSCs produce large numbers of neuroblasts that migrate a long distance into the olfactory bulb (OB) where they differentiate into local circuit interneurons. Here, we review a broad range of discoveries that have emerged from studies of postnatal V-SVZ neurogenesis: the identification of NSCs as a subpopulation of astroglial cells, the neurogenic lineage, new mechanisms of neuronal migration, and molecular regulators of precursor cell proliferation and migration. It has also become evident that V-SVZ NSCs are regionally heterogeneous, with NSCs located in different regions of the ventricle wall generating distinct OB interneuron subtypes. Insights into the developmental origins and molecular mechanisms that underlie the regional specification of V-SVZ NSCs have also begun to emerge. Other recent studies have revealed new cell-intrinsic molecular mechanisms that enable lifelong neurogenesis in the V-SVZ. Finally, we discuss intriguing differences between the rodent V-SVZ and the corresponding human brain region. The rapidly expanding cellular and molecular knowledge of V-SVZ NSC biology provides key insights into postnatal neural development, the origin of brain tumors, and may inform the development regenerative therapies from cultured and endogenous human neural precursors.
大量神经干细胞/前体细胞(NSCs)存在于位于侧脑室壁的脑室下区(V-SVZ)。V-SVZ神经干细胞产生大量神经母细胞,这些神经母细胞远距离迁移至嗅球(OB),并在那里分化为局部回路中间神经元。在此,我们综述了一系列来自对出生后V-SVZ神经发生研究的广泛发现:将神经干细胞鉴定为星形胶质细胞亚群、神经发生谱系、神经元迁移的新机制以及前体细胞增殖和迁移的分子调节因子。同样明显的是,V-SVZ神经干细胞在区域上具有异质性,位于脑室壁不同区域的神经干细胞产生不同的OB中间神经元亚型。对V-SVZ神经干细胞区域特化的发育起源和分子机制的见解也已开始显现。最近的其他研究揭示了新的细胞内在分子机制,这些机制使V-SVZ能够进行终身神经发生。最后,我们讨论了啮齿动物V-SVZ与相应人类脑区之间有趣的差异。V-SVZ神经干细胞生物学中迅速扩展的细胞和分子知识为出生后神经发育、脑肿瘤的起源提供了关键见解,并可能为从培养的和内源性人类神经前体细胞开发再生疗法提供信息。