Honig L S, Herrmann K, Shatz C J
Department of Neurobiology, Stanford University Medical Center, CA 94305, USA.
Cereb Cortex. 1996 Nov-Dec;6(6):794-806. doi: 10.1093/cercor/6.6.794.
The developing human cerebral cortex is distinguished by a particularly wide subplate, a transient zone in which crucial cell-cell interactions occur. To further understand the role of the subplate in human brain development, we have studied the immunohistochemical expression of certain neuronal (GAP-43, MAP-2, parvalbumin) and astroglial (vimentin, GFAP) markers in the developing visual cortex from gestational ages of 14 weeks to 9 months post-term. At 14-22 weeks, immunoreactivity to GAP-43, a protein involved in axonal outgrowth, was most prominent in the subplate and marginal zone neuropil and in the fibers of the radiations running near the ventricular zone; at 22-42 weeks, GAP-43 immunoreactive fibers were observed in the maturing cortical plate. Immunoreactivity for the microtubule-associated protein MAP-2 was present in the differentiating cortical plate at 14 weeks, but at 22-42 weeks was most prominent in the somata and dendrites of differentiated neurons, particularly the Cajal-Retzius neurons of the marginal zone, in neurons of the subplate and in those forming cortical layer 5. Parvalbumin immunoreactivity did not appear until 26 weeks, when stained neurons were in a sparse band of cells in layer 6 and upper subplate. Vimentin and GFAP did not stain differentiated neuronal cells. Vimentin immunoreactivity appeared early in neuroepithelial and radial glial cells, decreasing after 35 weeks, with a concomitant increase in GFAP immunoreactivity in radial glial and maturing astrocytic cells. Our results show that despite the greater complexity of the developing human neocortex, molecular markers are expressed in spatial and temporal patterns similar to those observed in non-human primates, carnivores and rodents. These protein markers should prove useful in developmental staging, and in providing a framework in which to examine congenital disorders of cerebral development.
发育中的人类大脑皮层的特点是具有特别宽的亚板层，这是一个关键的细胞间相互作用发生的过渡区域。为了进一步了解亚板层在人类大脑发育中的作用，我们研究了从孕14周到足月后9个月的发育中的视觉皮层中某些神经元（生长相关蛋白43、微管相关蛋白2、小白蛋白）和星形胶质细胞（波形蛋白、胶质纤维酸性蛋白）标志物的免疫组化表达。在14 - 22周时，与轴突生长有关的蛋白生长相关蛋白43的免疫反应性在亚板层和边缘区神经毡以及靠近脑室区的放射状纤维中最为显著；在22 - 42周时，在成熟的皮质板中观察到生长相关蛋白43免疫反应性纤维。微管相关蛋白2的免疫反应性在14周时出现在分化中的皮质板中，但在22 - 42周时，在分化神经元的胞体和树突中最为显著，特别是边缘区的卡哈尔-雷茨乌斯神经元、亚板层的神经元以及形成皮质第5层的神经元。小白蛋白免疫反应性直到26周才出现，此时染色的神经元位于第6层和上层亚板层的稀疏细胞带中。波形蛋白和胶质纤维酸性蛋白不染色分化的神经元细胞。波形蛋白免疫反应性在神经上皮细胞和放射状胶质细胞中早期出现，35周后下降，同时放射状胶质细胞和成熟星形胶质细胞中的胶质纤维酸性蛋白免疫反应性增加。我们的结果表明，尽管发育中的人类新皮层更为复杂，但分子标志物的表达在时空模式上与在非人灵长类动物、食肉动物和啮齿动物中观察到的相似。这些蛋白质标志物在发育分期以及为研究先天性脑发育障碍提供一个框架方面应该是有用的。
