Hu Ting, Kong Yifan, Tan Yulian, Ma Pengcheng, Wang Jianhong, Sun Xuelian, Xiang Kun, Mao Bingyu, Wu Qingfeng, Yi Soojin V, Shi Lei
Key Laboratory of Genetic Evolution & Animal Models, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650201, China.
Key Laboratory of Animal Models and Human Disease Mechanisms of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China.
bioRxiv. 2024 Dec 9:2024.12.08.627376. doi: 10.1101/2024.12.08.627376.
Neocortex expansion has a concerted relationship with folding, underlying evolution of human cognitive functions. However, molecular mechanisms underlying this significant evolutionary process remains unknown. Here, using tree shrew as an outgroup of primates, we identify a new regulator which acquired its expression before the emergence of primates. Following the evolution of cis-regulatory elements, the CCNB1IP1 expression has steadily increased over the course of primate brain evolution, mirroring the gradual increase of neocortex. Mechanistically, we elucidated that CCNB1IP1 expression can cause an increase in neural progenitors through shortening G1 phase. Consistently, the CCNB1IP1 knock-in mouse model exhibited traits associated with enhanced learning and memory abilities. Together, our study reveals how changes in expression may have contributed to the gradual evolution in primate brain.
新皮质扩张与折叠存在协同关系，这是人类认知功能进化的基础。然而，这一重要进化过程背后的分子机制仍不清楚。在这里，我们以树鼩作为灵长类动物的外类群，鉴定出一种在灵长类动物出现之前就已获得表达的新调节因子。随着顺式调控元件的进化，CCNB1IP1的表达在灵长类动物大脑进化过程中稳步增加，这与新皮质的逐渐增加相呼应。从机制上讲，我们阐明CCNB1IP1的表达可通过缩短G1期导致神经祖细胞增加。一致的是，CCNB1IP1基因敲入小鼠模型表现出与学习和记忆能力增强相关的特征。总之，我们的研究揭示了表达变化可能如何促成了灵长类动物大脑的逐渐进化。
