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Evolution of CCNB1IP1 regulating emergence and increase of cortical folding in primates

ABSTRACT: Cortical expansion and folding have gradually increased during primate evolution, reaching the highest in the human brain. Indeed, cortical folding has a concerted relationship with neocortex expansion, underlying evolution of human cognitive functions. However, molecular mechanisms underlying concerted evolution remain largely unknown. Here, using Chinese tree shrew as an outgroup of primate, we identify the Cyclin B1 Interacting Protein 1 gene CCNB1IP1 (also named HEI10) as a key regulator of cortically concerted evolution. CCNB1IP1 has acquired brain expression in primates, and is highly expressed in human neuronal progenitor cells. The expression of CCNB1IP1 has gradually increased along primate brain evolution, coinciding with the increase of cortical size and folding. Mechanistically, we elucidated that overexpression of CCNB1IP1, leading to a decrease of G1 duration, and subsequently causes an increase in basal progenitors and neurons. Furthermore, we generated a novel CCNB1IP1 knock-in mouse model and provide confirmation that CCNB1IP1 can induce cortical folding in otherwise smooth mouse brain. Moreover, the CCNB1IP1 knock-in mouse model exhibited traits associated with enhanced learning and memory abilities. Together, our study reveals how the changes in CCNB1IP1 expression may have contributed to the increase of cortical size and folding during human brain evolution.

ORGANISM(S): Tupaia belangeri chinensis

PROVIDER: GSE247966 | GEO | 2026/07/29

REPOSITORIES: GEO

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