Nowakowski Richard S, Caviness Verne S, Takahashi Takao, Hayes Nancy L
Department of Neuroscience and Cell Biology, UMDNJ-Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, New Jersey 08854, USA.
Results Probl Cell Differ. 2002;39:1-25. doi: 10.1007/978-3-540-46006-0_1.
During the development of the neocortex, cell proliferation occurs in two specialized zones adjacent to the lateral ventricle. One of these zones, the ventricular zone, produces most of the neurons of the neocortex. The proliferating population that resides in the ventricular zone is a pseudostratified ventricular epithelium (PVE) that looks uniform in routine histological preparations, but is, in fact, an active and dynamically changing population. In the mouse, over the course of a 6-day period, the PVE produces approximately 95% of the neurons of the adult neocortex. During this time, the cell cycle of the PVE population lengthens from about 8 h to over 18 h and the progenitor population passes through a total of 11 cell cycles. This 6-day, 11-cell cycle period comprises the "neuronogenetic interval" (NI). At each passage through the cell cycle, the proportion of daughter cells that exit the cell cycle (Q cells) increases from 0 at the onset of the NI to 1 at the end of the NI. The proportion of daughter cells that re-enter the cell cycle (P cells) changes in a complementary fashion from 1 at the onset of the NI to 0 at the end of the NI. This set of systematic changes in the cell cycle and the output from the proliferative population of the PVE allows a quantitative and mathematical treatment of the expansion of the PVE and the growth of the cortical plate that nicely accounts for the observed expansion and growth of the developing neocortex. In addition, we show that the cells produced during a 2-h window of development during specific cell cycles reside in a specific set of laminae in the adult cortex, but that the distributions of the output from consecutive cell cycles overlap. These dynamic events occur in all areas of the PVE underlying the neocortex, but there is a gradient of maturation that begins in the rostrolateral neocortex near the striatotelencephalic junction and which spreads across the surface of the neocortex over a period of 24-36 h. The presence of the gradient across the hemisphere is a possible source of positional information that could be exploited during development to establish the areal borders that characterize the adult neocortex.
在新皮质发育过程中，细胞增殖发生在与侧脑室相邻的两个特殊区域。其中一个区域，即脑室区，产生了新皮质的大部分神经元。位于脑室区的增殖群体是假复层脑室上皮（PVE），在常规组织学切片中看起来是均匀的，但实际上是一个活跃且动态变化的群体。在小鼠中，在6天的时间里，PVE产生了约95%的成年新皮质神经元。在此期间，PVE群体的细胞周期从约8小时延长至超过18小时，祖细胞群体总共经历11个细胞周期。这个6天、11个细胞周期的阶段构成了“神经元发生间隔”（NI）。在每次通过细胞周期时，退出细胞周期的子细胞（Q细胞）比例从NI开始时的0增加到NI结束时的1。重新进入细胞周期的子细胞（P细胞）比例则以互补的方式从NI开始时的1变化到NI结束时的0。PVE增殖群体在细胞周期和输出方面的这一系列系统性变化，使得对PVE的扩展以及皮质板的生长进行定量和数学处理成为可能，这很好地解释了发育中的新皮质所观察到的扩展和生长。此外，我们表明，在特定细胞周期的2小时发育窗口期间产生的细胞，在成年皮质中位于特定的一组层中，但连续细胞周期的输出分布存在重叠。这些动态事件发生在新皮质下方PVE的所有区域，但存在一个成熟梯度，该梯度始于靠近纹状体 - 端脑交界处的前外侧新皮质，并在24 - 36小时内遍布新皮质表面。半球上这种梯度的存在可能是一种位置信息来源，在发育过程中可被利用来建立表征成年新皮质的区域边界。
