Eşiyok Nesil, Liutikaite Neringa, Haffner Christiane, Peters Jula, Heide Sabrina, Oegema Christina Eugster, Huttner Wieland B, Heide Michael
German Primate Center, Leibniz Institute for Primate Research, Kellnerweg 4, D-37077 Göttingen, Germany.
Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, D-01307 Dresden, Germany.
Sci Adv. 2025 Mar 28;11(13):eads7543. doi: 10.1126/sciadv.ads7543. Epub 2025 Mar 26.
We determined the roles of two coevolved and coexpressed human-specific genes, and , on the abundance of the cortical progenitors that underlie the evolutionary expansion of the neocortex, the seat of higher cognitive abilities in humans. Using automated microinjection into apical progenitors (APs) of embryonic mouse neocortex and electroporation of APs in chimpanzee cerebral organoids, we show that promotes the delamination of AP progeny, by promoting oblique cleavage plane orientation during AP division, leading to increased abundance of the key basal progenitor type, basal radial glia. In contrast, promotes AP proliferation, leading to expansion of the AP pool. When expressed together, and exert coordinated effects, resulting in expansion of basal progenitors while maintaining self-renewal of APs. Hence, these two human-specific genes orchestrate the behavior of APs, and the lineages of their progeny, in a manner essential for the evolutionary expansion of the human neocortex.
我们确定了两个共同进化且共同表达的人类特异性基因，即[基因名称1]和[基因名称2]，在构成新皮层进化扩张基础的皮质祖细胞数量方面所起的作用。新皮层是人类高级认知能力的所在部位。通过对胚胎小鼠新皮层的顶端祖细胞（APs）进行自动显微注射以及对黑猩猩大脑类器官中的APs进行电穿孔，我们发现[基因名称1]通过促进AP分裂过程中倾斜分裂平面的定向，从而促进AP子代的脱层，导致关键的基底祖细胞类型——基底放射状胶质细胞的数量增加。相比之下，[基因名称2]促进AP增殖，导致AP池的扩大。当共同表达时，[基因名称1]和[基因名称2]发挥协同作用，导致基底祖细胞扩张，同时维持AP的自我更新。因此，这两个人类特异性基因以对人类新皮层进化扩张至关重要的方式协调AP及其子代谱系的行为。
