The Ritchie Centre, Hudson Institute of Medical Research, Monash University, Clayton, VIC 3168, Australia.
Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC 3168, Australia.
Cereb Cortex. 2020 Nov 3;30(12):6169-6190. doi: 10.1093/cercor/bhaa171.
Gyrification of the cerebral cortex is a developmentally important process, but the mechanisms that drive cortical folding are not fully known. Theories propose that changes within the cortical plate (CP) cause gyrification, yet differences between the CP below gyri and sulci have not been investigated. Here we report genetic and microstructural differences in the CP below gyri and sulci assessed before (at 70 days of gestational age [GA] 70), during (GA 90), and after (GA 110) gyrification in fetal sheep. The areal density of BDNF, CDK5, and NeuroD6 immunopositive cells were increased, and HDAC5 and MeCP2 mRNA levels were decreased in the CP below gyri compared with sulci during gyrification, but not before. Only the areal density of BDNF-immunopositive cells remained increased after gyrification. MAP2 immunoreactivity and neurite outgrowth were also increased in the CP below gyri compared with sulci at GA 90, and this was associated with microstructural changes assessed via diffusion tensor imaging and neurite orientation dispersion and density imaging at GA 98. Differential neurite outgrowth may therefore explain the localized changes in CP architecture that result in gyrification.
大脑皮层的脑回形成是一个发育过程中的重要过程，但驱动皮层折叠的机制尚未完全了解。有理论提出，皮层板（CP）内的变化导致脑回形成，但脑回和脑沟下方 CP 的差异尚未得到研究。在这里，我们报告了在胎儿羊的脑回形成之前（GA70 时 70 天）、期间（GA90 时）和之后（GA110 时），脑回和脑沟下方 CP 的遗传和微观结构差异。在脑回形成过程中，与脑沟相比，脑回下方 CP 中的 BDNF、CDK5 和 NeuroD6 免疫阳性细胞的面积密度增加，HDAC5 和 MeCP2 mRNA 水平降低，但在脑回形成之前并非如此。只有 BDNF 免疫阳性细胞的面积密度在脑回形成后仍然增加。在 GA90 时，MAP2 免疫反应和神经突生长也在脑回下方 CP 中比脑沟中增加，这与在 GA98 时通过弥散张量成像和神经突取向分散和密度成像评估的微观结构变化相关。因此，差异神经突生长可能解释了导致脑回形成的 CP 结构的局部变化。
