A Gene That Grew More Active in Primates Puts Folds in Mouse Brains

Researchers at the Kunming Institute of Zoology, part of the Chinese Academy of Sciences, report that a gene called CCNB1IP1 switched on in the primate brain and grew steadily more active as the cortex became larger and more folded, and that engineering the gene into mice produced folds in brains that are normally smooth. The work was published Sept. 29, 2026, in Nature Genetics.

The Nature Genetics paper says the gradual expansion and folding of the cortex, the brain's outer layer, are central to human cognitive evolution, and that the molecular reasons for it remain poorly understood.

To pick the gene out, the team compared primates with the tree shrew, a small mammal whose lineage sits just outside the primate group. In primates, the gene began to be used in the brain and its activity rose over evolutionary time, tracking the increase in cortical size and folding. A comparison of the DNA switches that control the gene points to changes in those switches as the reason for the rise.

Raising the gene's activity altered the cell cycle and increased the numbers of basal progenitors, the dividing cells that supply the cortex with neurons, and of neurons themselves. The authors report that CCNB1IP1 suppresses a protein called E2F1 by marking it for destruction inside the cell. Mice engineered to carry the gene developed cortical folding.

The authors call CCNB1IP1 a key regulator of human brain evolution. It is not the first gene tied to the size of the cortex: earlier work cited in the paper linked two human-specific genes, ARHGAP11B and NOTCH2NL, to the expansion of the cortex in development.

The sequencing data behind the study are deposited in NCBI's Gene Expression Omnibus, a public archive, and peer reviewer reports for the paper are available.