Tamamaki N, Nakamura K, Okamoto K, Kaneko T
Department of Morphological Brain Science, Graduate School of Medicine, Kyoto University, Yoshida Konoecho, Sakyoku, 606-8501, Kyoto, Japan.
Neurosci Res. 2001 Sep;41(1):51-60. doi: 10.1016/s0168-0102(01)00259-0.
Neocortical neurons are produced by cell division of neural stem cells in the ventricular zone of the cerebral cortex. We investigated the production of neurons by infecting neuroepithelial cells with a modified GFP-recombinant adenovirus. The adenovirus DNA is inherited by only one daughter cell at each cell division and travels one way from the progenitor to the progeny. Since the ventricular zone (VZ) of the embryo neocortex expressed an adenovirus receptor, CAR ubiquitously, morphology and cell-lineage of cells in the VZ could be revealed by the adenovirus infection. Radial glias, cells with a bipolar shape, and spherical cells were found as modified-GFP-positive (mGFP+) in the VZ. The bipolar cells (radial cells) had a radial process not in contact with the pia mater and a growth-cone-like structure at the edge of their radial process, while the radial glias had a process spanning all the cortical layers. Ten hours after viral infection, most mGFP+ cells were radial cells. In the following 8 h, the percentage of mGFP+ radial glias in mGFP+ neocortical cells increased from 18 to 50%, while that in radial/spherical cells decreased from 75 to 19%. The radial glias often divided asymmetrically and produced spherical cells and neuronal precursors. The spherical cells seemed to become radial cells by extending a radial process. The spherical cells, radial cells and radial glias seemed to constitute a proliferating cell cycle during which postmitotic neuronal precursors are produced. The neuronal precursors that inherited the radial processes migrated radially and developed into neocortical neurons. Four days after the viral infection, 97% of mGFP+ cells were neocortical neurons. Here, we propose that the radial glia is a progenitor of neocortical neurons, and that a significant number of radially migrating neurons is guided by their own radial processes connected to the pia mater.
新皮质神经元由大脑皮质脑室区神经干细胞的细胞分裂产生。我们通过用修饰的绿色荧光蛋白重组腺病毒感染神经上皮细胞来研究神经元的产生。腺病毒DNA在每次细胞分裂时仅由一个子细胞继承，并从祖细胞单向传递到子代细胞。由于胚胎新皮质的脑室区（VZ）普遍表达腺病毒受体CAR，通过腺病毒感染可以揭示VZ中细胞的形态和细胞谱系。在VZ中发现呈双极形状的放射状胶质细胞和球形细胞为修饰绿色荧光蛋白阳性（mGFP+）。双极细胞（放射状细胞）有一个不与软脑膜接触的放射状突起，在其放射状突起边缘有一个生长锥样结构，而放射状胶质细胞有一个跨越所有皮质层的突起。病毒感染10小时后，大多数mGFP+细胞是放射状细胞。在接下来的8小时内，mGFP+新皮质细胞中mGFP+放射状胶质细胞的百分比从18%增加到50%，而在放射状/球形细胞中的百分比从75%下降到19%。放射状胶质细胞常进行不对称分裂，产生球形细胞和神经元前体。球形细胞似乎通过延伸放射状突起而变成放射状细胞。球形细胞、放射状细胞和放射状胶质细胞似乎构成一个增殖细胞周期，在此期间产生有丝分裂后的神经元前体。继承了放射状突起的神经元前体沿放射状迁移并发育为新皮质神经元。病毒感染4天后，97%的mGFP+细胞是新皮质神经元。在此，我们提出放射状胶质细胞是新皮质神经元的祖细胞，并且大量沿放射状迁移的神经元由其与软脑膜相连的自身放射状突起引导。
