Wednesday, January 26

Neurosciences of the UMH of Elche identifies which molecule is responsible for the size of the human brain

What determines the size of the brain? The group of Neurogénesis Y Cortical Expansion, lead by Victor Borrell, of the Institute of Neurosciences UMH of Elche and the Superior Council of Scientific Investigations has come to the conclusion that ‘the fault’ lies with a small genetic material, contained in ribonucleic acid, a molecule called MIR3607, which is activated during embryonic development in mammals with very large brains, such as humans, and remains off in those with small brains, such as mice. “Its main function is to increase the number of neural stem cells to enhance the formation of neurons,” say the researchers. “MIR3607 during embryonic development was selected by evolution to enhance in most mammals the expansion of the cerebral cortex, the most evolved part of the brain.” In contrast, in rodents the loss of this microRNA led to a small and smooth brain, unlike most mammals, “which evolved into large and folded brains”, concludes the study published yesterday in the journal Science Advances.

The number of specific and exclusive genes in humans is relatively small, while the number of genes conserved and expressed in the cerebral cortex in different mammalian species during embryonic development is much higher. A fundamental question still to be resolved was how the expression of these highly conserved genes that guide the development of the cerebral cortex has been regulated so differently during evolution in different species.

The scientific paper, focusing on a gene that gives rise to a microRNA, has found that, in species with small brains, the loss of expression, or ‘silencing’, of MIR3607 during evolution ‘led to a dramatic decrease in the size of its brain. cerebral cortex, which ultimately determines the size of the brain. Also, your cerebral cortex turned smooth, compared to most of the mammals, which has been increasing its surface by convolutions and sulci, like a relief of peaks and valleys ».

Archive image of the Brain Week workshops of the Institute of Neurosciences. | RAFA ARJONES B.CAMPOY / M.ALARCÓNB.C.

The genetic mechanisms underlying this secondary loss in the evolution of the rodent brain were completely unknown until now. «With our work we show that the microRNA MIR3607 is expressed embryo in the large cerebral cortex of primates and carnivores, like the ferret, but not in the mouse ”, says Victor Borrell.

MicroRNAs (miRNAs) are small RNAs that do not give rise to proteins, but rather regulate the expression of other genes, which is why they are essential during embryonic development. In fact, the evolution of animal species parallels the appearance of new miRNAs “that have promoted diversity during embryonic development.” However, despite the ability of miRNAs to modulate gene expression, they have surprisingly received little attention in the context of brain evolution and expansion.

«With this work we have identified MIR3607 as a important regulator of the signaling cascade, a road with key functions in the embryonic development of the cerebral cortex because it regulates processes such as the proliferation of stem cells and cell differentiation. Our findings also dovetail with recent discoveries about the importance of miRNAs in early cortical development“Explains Dr. Borrell. The artificial expression of MIR3607, from a DNA vector developed by Dr. Borrell’s group in the cerebral cortex of mouse embryos, made it possible to find out that the expression of this microRNA is in itself sufficient to promote the expansion of the area. ventricular cell of the brain, the layer where the stem cells that generate neurons are born. In addition, they confirmed that it also causes expansion of these stem cells.

An expansion that was invested in monkeys and mice

The evolution in mammals towards the expansion and folding of the cerebral cortex was reversed in monkeys and rodents, and their brains evolved becoming smaller and smoother than those of their ancestors. “Our results identify for the first time that the loss of MIR3607 was selected during the evolution of small mammals, to decrease the size of the cerebral cortex,” highlights Borrell.

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