Physiological Genomics, Institute of Physiology, Ludwig-Maximilian University Munich, Munich, Germany.
Cell. 2013 Apr 25;153(3):535-49. doi: 10.1016/j.cell.2013.03.027.
Evolution of the mammalian brain encompassed a remarkable increase in size of the cerebral cortex, which includes tangential and radial expansion. However, the mechanisms underlying these key features are still largely unknown. Here, we identified the DNA-associated protein Trnp1 as a regulator of cerebral cortex expansion in both of these dimensions. Gain- and loss-of-function experiments in the mouse cerebral cortex in vivo demonstrate that high Trnp1 levels promote neural stem cell self-renewal and tangential expansion. In contrast, lower levels promote radial expansion, with a potent increase of the number of intermediate progenitors and basal radial glial cells leading to folding of the otherwise smooth murine cerebral cortex. Remarkably, TRNP1 expression levels exhibit regional differences in the cerebral cortex of human fetuses, anticipating radial or tangential expansion. Thus, the dynamic regulation of Trnp1 is critical to control tangential and radial expansion of the cerebral cortex in mammals.
哺乳动物大脑的进化包括大脑皮层的显著增大，其中包括切向和放射状扩张。然而，这些关键特征的机制在很大程度上仍然未知。在这里，我们确定 DNA 相关蛋白 Trnp1 是这两个维度中大脑皮层扩张的调节因子。在体内的小鼠大脑皮层中进行的功能获得和功能丧失实验表明，高 Trnp1 水平促进神经干细胞自我更新和切向扩张。相比之下，较低的水平促进放射状扩张，中间祖细胞和基底放射状胶质细胞的数量大量增加，导致原本光滑的小鼠大脑皮层折叠。值得注意的是，TRNP1 表达水平在人类胎儿大脑皮层中存在区域差异，预示着放射状或切向扩张。因此，Trnp1 的动态调节对于控制哺乳动物大脑皮层的切向和放射状扩张至关重要。
