Chinese researchers discovered a mechanism by which an ancient gene regulates the formation of brain folds in humans. The study, published in Nature Genetics, was led by Shi Lei to explore how highly conserved genes influence human brain evolution.
The team compared transcriptomic data from the embryonic cerebral cortex of humans, macaques, marmosets, tree shrews and mice. Analysis showed that the ancient gene CCNB1IP1 was expressed at low levels in the brains of tree shrews.
Expression levels of CCNB1IP1 increased stepwise across tree shrews, marmosets, macaques and humans, reaching a peak in the human brain. Marmosets with smooth brains showed CCNB1IP1 levels similar to tree shrews, while macaques with folded brains exhibited markedly higher expression.
"The expression level of this ancient gene is closely correlated with the degree of cortical folding," said Shi. Researchers identified a regulatory sequence called CRE1 that drives this elevated expression of CCNB1IP1.
A mouse model carrying the gene was constructed to test these findings. Mice with the knock-in gene developed cortical folding structures and showed improved learning and memory in behavioral tests.
