Javaherian Ashkan, Kriegstein Arnold
Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA 94143, USA.
Cereb Cortex. 2009 Jul;19 Suppl 1(Suppl 1):i70-7. doi: 10.1093/cercor/bhp029. Epub 2009 Apr 3.
The excitatory neurons of the mammalian cerebral cortex arise from asymmetric divisions of radial glial cells in the ventricular zone and symmetric division of intermediate progenitor cells (IPCs) in the subventricular zone (SVZ) of the embryonic cortex. Little is known about the microenvironment in which IPCs divide or whether a stem cell niche exists in the SVZ of the embryonic cortex. Recent evidence suggests that vasculature may provide a niche for adult stem cells but its role in development is less clear. We have investigated the vasculature in the embryonic cortex during neurogenesis and find that IPCs are spatially and temporally associated with blood vessels during cortical development. Intermediate progenitors mimic the pattern of capillaries suggesting patterns of angiogenesis and neurogenesis are coordinated during development. More importantly, we find that IPCs divide near blood vessel branch points suggesting that cerebral vasculature establishes a stem cell niche for intermediate progenitors in the SVZ. These data provide novel evidence for the presence of a neurogenic niche for intermediate progenitors in the embryonic SVZ and suggest blood vessels are important for proper patterning of neurogenesis.
哺乳动物大脑皮层的兴奋性神经元起源于脑室区放射状胶质细胞的不对称分裂以及胚胎皮层室下区(SVZ)中间祖细胞(IPC)的对称分裂。关于IPC分裂所处的微环境,或者胚胎皮层SVZ中是否存在干细胞龛,我们了解得很少。最近的证据表明,脉管系统可能为成体干细胞提供龛位,但其在发育过程中的作用尚不清楚。我们研究了神经发生过程中胚胎皮层的脉管系统,发现IPC在皮层发育过程中在空间和时间上与血管相关。中间祖细胞模仿毛细血管的模式,这表明血管生成和神经发生的模式在发育过程中是协调的。更重要的是,我们发现IPC在血管分支点附近分裂,这表明脑脉管系统为SVZ中的中间祖细胞建立了一个干细胞龛。这些数据为胚胎SVZ中存在中间祖细胞的神经源性龛提供了新的证据,并表明血管对于神经发生的正确模式形成很重要。