miRNA responsible for large size in human cerebral cortex

The number of specific genes unique to humans is relatively small, whereas the number of genes conserved and expressed in the cerebral cortex of different mammals during embryonic development is much higher
.

A fundamental unresolved question is how these highly conserved genes regulate the development of the cerebral cortex during the evolution of different species

In a paper published in the journal Science Advances, researchers from the Spanish National Research Council, Miguel Hernández University and the Alicante Neuroscience Institute, under the leadership of Dr.
Víctor Borrell, focused on the study of a gene called The microRNA gene of MIR3607
.

They also found that, in species with smaller brains, evolutionary loss or "silencing" of MIR3607 led to a dramatic reduction in the size of the cerebral cortex, which ultimately determines brain size

In addition, the cerebral cortex becomes smooth, whereas the cerebral cortex of most mammals increases the surface area through the gyri and sulci, in an undulating fashion
.

Until now, the genetic mechanism of this secondary loss in rodent brain evolution was completely unknown

MicroRNAs (miRNAs) are small RNAs that do not produce proteins but regulate the expression of other genes, which is why they are essential during embryonic development
.

However, despite their ability to regulate gene expression, miRNAs have surprisingly received little attention in the context of brain evolution and expansion

"Through this work, we have identified MIR3607 as an important regulator of the Wnt/β-Catenin signaling cascade, a pathway with key functions in embryonic development of the cerebral cortex as it regulates processes such as stem cell proliferation and cell differentiation
.

We The findings are also in line with recent findings on the importance of miRNAs in early cortical development, regulating the expansion of neural stem cells and the homeostasis of the germ layer from which they arise," explained Dr.

evolutionary frustration

From an evolutionary perspective, this finding suggests that "loss of MIR3607 expression in the developing cerebral cortex may be a key factor in the quadratic reduction in brain size during rodent evolution
.

Loss of MIR3607 in the embryonic mouse cerebral cortex suggests that The crucial and unanswered question of how its activation is regulated," explains Kaviya Chinnappa, first author of the paper

The general evolutionary trend of the expansion and folding of the mammalian cerebral cortex has reversed in some mammalian groups, such as New World monkeys, and especially rodents, which evolved to have smaller and smoother brains than their ancestors
.

"Our results confirm for the first time that the loss of MIR3607 was selected during small mammal evolution to reduce the size of the mouse cerebral cortex," Borrell said

"MicroRNAs are generally highly conserved across animal species.
The similarity of
MIR3607 in humans, macaques, ferrets and mice suggests that this microRNA has a conserved function in the mouse brain
.

Therefore, we reasoned that if we Experimentally re-expressing MIR3607 in the mouse embryonic brain, we could elucidate its role in cortical development," explains Chinnappa

Artificial expression of MIR3607 from a DNA vector developed by Dr.
Borrell's team in the mouse embryonic cerebral cortex showed that expression of this microRNA alone is sufficient to promote the expansion of the brain's ventricular region, where neuron-producing stem cells are born
.
Furthermore, they demonstrated that overexpression of MIR3607 in human brain organoids also leads to the expansion of these stem cells
.

---

---

Magazine

Science Advances

DOI

10.
1126\sciadv.
abj4010