Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
Czech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, Vestec, Czech Republic.
EMBO J. 2021 Jul 1;40(13):e107093. doi: 10.15252/embj.2020107093. Epub 2021 May 3.
Neocortex expansion during human evolution provides a basis for our enhanced cognitive abilities. Yet, which genes implicated in neocortex expansion are actually responsible for higher cognitive abilities is unknown. The expression of human-specific ARHGAP11B in embryonic/foetal mouse, ferret and marmoset neocortex was previously found to promote basal progenitor proliferation, upper-layer neuron generation and neocortex expansion during development, features commonly thought to contribute to increased cognitive abilities. However, a key question is whether this phenotype persists into adulthood and if so, whether cognitive abilities are indeed increased. Here, we generated a transgenic mouse line with physiological ARHGAP11B expression that exhibits increased neocortical size and upper-layer neuron numbers persisting into adulthood. Adult ARHGAP11B-transgenic mice showed altered neurobehaviour, notably increased memory flexibility and a reduced anxiety level. Our data are consistent with the notion that neocortex expansion by ARHGAP11B, a gene implicated in human evolution, underlies some of the altered neurobehavioural features observed in the transgenic mice, such as the increased memory flexibility, a neocortex-associated trait, with implications for the increase in cognitive abilities during human evolution.
人类进化过程中的新皮层扩张为我们增强的认知能力提供了基础。然而，哪些与新皮层扩张相关的基因实际上负责更高的认知能力尚不清楚。先前发现，人类特异性 ARHGAP11B 在胚胎/胎儿小鼠、雪貂和狨猴新皮层中的表达促进了发育过程中的基底前体细胞增殖、上层神经元生成和新皮层扩张，这些特征通常被认为有助于提高认知能力。然而，一个关键问题是这种表型是否会持续到成年期，如果是，认知能力是否确实会提高。在这里，我们生成了一条具有生理 ARHGAP11B 表达的转基因小鼠系，其具有持续到成年的新皮层增大和上层神经元数量增加的表型。成年 ARHGAP11B 转基因小鼠表现出改变的神经行为，特别是记忆灵活性增加和焦虑水平降低。我们的数据与以下观点一致，即 ARHGAP11B 的新皮层扩张，该基因与人类进化有关，是转基因小鼠中观察到的一些改变的神经行为特征的基础，例如增加的记忆灵活性，与新皮层相关的特征，这对人类进化过程中认知能力的提高具有重要意义。
