Human SERPINA3 induces neocortical folding and improves cognitive ability in mice

Neocortex expansion and folding are related to human intelligence and cognition, but the molecular and cellular mechanisms underlying cortical folding remain poorly understood. Here, we report that the human gene SERPINA3 is linked to gyrification. Specifically, the overexpression of SERPINA3 induced neocortical folding, increased the abundance of neurons, and improved cognitive abilities. Further, SERPINA3 promoted proliferation of the outer radial glia (oRG, also referred to as the basal radial glia) and increased the number of upper-layer neurons. The downstream target Glo1 was determined to be involved in SERPINA3-induced gyrification. Moreover, SERPINA3 increased the proliferation of oRG by binding to the Glo1 promoter. Assessment of behavior performance showed enhanced cognitive abilities in SERPINA3 knock-in mice. Our findings will enrich the understanding of neocortical expansion and gyrification and provide insights into possible treatments for intellectual disability and lissencephaly syndrome.

Automated summary

Neocortex expansion and folding are linked to human intelligence and cognition. The study discovered that the overexpression of the SERPINA3 gene can induce neocortical folding, increase neuron abundance, and improve cognitive abilities. Further investigation revealed that SERPINA3 promotes the proliferation of outer radial glia and affects cortical folding.