The research group of Jiao Jianwei of the Institute of Zoology revealed a new mechanism of human specific genes to promote cerebral cortex folding

In the process of human evolution, the expansion of the neocortex is closely related
to the improvement of intelligence and cognitive function.
A key aspect of this expansion is the formation of the cerebral cortical sulcus gyrus, which allows the dilated cortical surface area to accommodate the limited skull space
.
These evolutionary features rely primarily on a larger number of cortical neurons produced by multiple neural stem and progenitor cell subtypes and their neurogenic
division.
In recent years, many studies have revealed that external radial glial cells (oRG) have an important connection with the formation of cerebral cortical gyrus, one is because oRG as a large number of nerve precursor cells in the human brain, increasing the type and number of neural progenitor cells, and the other is that oRG provides more radial migration paths for neurons, thereby promoting the expansion of the cortex and the formation
of the sulcus.
However, the molecular and cellular mechanisms underlying the folding of the cerebral cortex are still poorly
understood.

On November 22, 2022, the research group of Jiao Jianwei of the Institute of Zoology, Chinese Academy of Sciences published a report entitled Human SERPINA3 induces neocortical folding and improves cognitive ability in mice in the journal Cell Discovery Research papers
.
This study found that the human-derived gene SERPINA3 promoted the expansion and folding of the mouse cortex, increased the number of upper neurons, and significantly improved the cognitive ability
of the mice.

First, conditional knock-in mice (cKI) were constructed, which overexpressed SERPINA3 in the nervous system, and it was found that SERPINA3 can promote the proliferation of neural stem cells and the production
of oRG in the mouse brain during neurodevelopment.
After birth, cKI mice showed the phenomenon of enlargement of cerebral cortex surface area, thickening of cortex, and formation of sulcus structure
.
Single-cell sequencing analysis of the cerebral cortex of neonatal mice further demonstrated that SERPINA3 overexpression increased the output
of upper neurons.
Adult cKI mice showed stronger learning and memory abilities in behavioral experiments than wild types
.

Studies using transcriptome sequencing also found that SERPINA3 regulates its expression
by binding to the promoter of the downstream target gene Glo1.
As a key factor in regulating the metabolism of pyruvaldehyde, the expression of Glo1 accelerates the metabolism of pyruvaldehyde after upregulation, thereby promoting the proliferation of neural progenitor cells and the expansion and folding
of the cerebral cortex.

In summary, this study not only reveals the important role of SERPINA3 on the proliferation and abundance of neural stem cells, but also elucidates a new molecular mechanism
of cerebral cortex expansion and folding.

Professor Jiao Jianwei of the Institute of Zoology, Chinese Academy of Sciences is the corresponding author of the paper, and doctoral students Zhao Jinyue and Feng Chao are the co-first authors
of the paper.
The research was funded
by the Ministry of Science and Technology, the National Natural Science Foundation of China, and the Academy of Sciences.

Original link:

Diagram of the action pattern of SERPINA3 in cerebral cortical expansion and folding