A group of Chinese scientists has revealed the mechanism regulating the development of brain folds through an ancient gene, shedding new light on the evolution of the human brain. These findings were recently published in the journal Nature Genetics.
The human brain is covered with complex folds and grooves, which are one of the most important biological foundations for the emergence of complex human cognitive functions. Traditionally, it was believed that the expansion of primate cerebral cortex was primarily due to new, evolved genes.
However, a research team led by Shi Lei, a specialist from the Kunming Institute of Zoology, Chinese Academy of Sciences, proposed an alternative hypothesis. According to this version, certain ancient and highly conserved genes may also play a key role in the evolution of the human brain by altering their expression levels through modifications to regulatory elements.
The team compared transcriptomic data from different layers of embryonic mouse cortex, shrew, marmoset, macaque, and human brains. They found that an ancient gene called 'CCNB1IP1' was already expressed in the shrew brain, a close relative of primates, long before the appearance of primates, but at a relatively low level of expression.
Furthermore, the team discovered that during subsequent evolution, the expression level of this ancient gene showed a clear stepwise increase among shrews, marmosets, macaques, and humans, reaching the highest level in the human brain.
Shi noted that 'the expression level of this ancient gene correlates closely with the degree of cortical folding.' He added that in marmosets, whose brains are smooth, the gene's expression level is similar to that in shrews. In macaques, whose brains have folds, the expression level is significantly increased, and in the human brain, it reaches its highest value.
Additionally, the researchers identified a key regulatory sequence, named CRE1, responsible for increasing CCNB1IP1 expression.
To test the gene's function, the team created a mouse model carrying this gene. The experiment showed that mice that normally have a smooth cerebral cortex developed cortical folding structures after the gene was introduced. Moreover, the modified mice demonstrated improved learning and memory abilities in behavioral tests.
The scientists emphasized that this study not only offers a new perspective on understanding the evolution of the human brain but also provides new clues for studying the causes of neurodevelopmental disorders.