2023-04-22 06:00:00
As its name suggests, the cerebral cortex covers the brain and gives it its typical rough appearance. It is one of the greatest wonders of nature, which has allowed us to go from using the simplest tools of our ancestors to creating tools as complex as a laptop or an international space station.
Thanks to the cerebral cortex we can build from the largest and most efficient buildings to the most beautiful cathedrals. We can have highly subtle social interactions and be able to identify a new type of virus like SARS-CoV-2 in record time and develop an effective vaccine against it.
Moreover, in the cerebral cortex resides a large part of what makes each one of us unique: our personality.
This is how our cerebral cortex evolved
Like our hands and nose, our cerebral cortex is the product of millions of years of evolution. after the great extinction of the dinosaurs 66 million years ago, the largest surviving mammals were not much larger than a vole, and their cerebral cortex weighed a few grams.
However, the incessant action of multiple factors continued to create mutations in the genome of these primitive mammals, just as it had been happening since the origin of life.
Some of these mutations were harmful (such as those that cause skin cancer, for example), and were lost when their carriers died. But other genetic mutations were beneficial, and were perpetuated in the following generations.
Through this process repeated over millions of generations, the small and relatively simple cerebral cortex of those early mammals was increasing in size and complexity until it became the phenomenal organ that occupies our skulls today and allows us to understand this article.
Well, a study carried out from the Institute of Neurosciences in Alicante has discovered one of these genetic changes that took place during evolution and that they were key to the expansion of the human cerebral cortex.
The cortex is formed during embryonic development from neural stem cells, which constantly divide giving rise to two daughter cells after each division. Early in development, the division of neural stem cells generates more stem cells, thus increasing in number.
From a certain moment on, they begin to generate neurons (neurogenesis), which will eventually form the adult cerebral cortex.
This is a critical step, because when cell division produces two neurons, there is no spare stem cell left that can continue to produce more neurons.
Thus, the total number of neurons in the cortex depends on the number of neural stem cells that they have to generate. And the more neurons that are generated and the more diverse they are, the greater the size and complexity of the cerebral cortex.
In the human embryonic brain the number of neural stem cells, their diversity and their proliferative capacity are enormous, while in the small mouse embryo they are much less.
A gene that regulates brain stem cells
New research in the lab shows that the high proliferative capacity of neural stem cells in the human cortex, and in other species with large cortex, is due in large part to gen MIR3607whose function remained completely unknown until now.
This gene belongs to the family of micro RNAs, small RNA sequences that act as little orchestra conductors, regulating the activity of other genes. In this case, MIR3607 increases proliferation of cortical stem cells so that they eventually generate a greater number of neurons.
The team has reached this conclusion by analyzing the presence and function of this microRNA during the embryonic development of the cerebral cortex in multiple large-brained mammalian species. Our study has included the human being, by culturing ‘mini-brains’ (brain organoids).
MIR3607 increases the proliferation of cortical stem cells so that they eventually generate a greater number of neurons
Why didn’t other mammals develop such complex cerebral cortices?
Evolution can be capricious and does not always progress towards larger and more complex organs or structures. Sometimes it makes them simpler or even eliminates them.
This is called secondary lossand the case of dolphins, whales and other marine mammals is known for which it was more useful to swim with agility to convert articulated arms and legs, and hands with fingers, into simple fins.
Similarly, when rodents diverged from primates 75 million years ago, their evolution led them to reduce the size of the cerebral cortex compared to their common primate ancestor.
What genetic changes and mutations caused this reduction in brain size in rodents?
This study answers this enigma for the first time. It turns out that MIR3607 is not expressed in rodents during embryonic development, unlike primates. That makes their neural stem cells not proliferate as much. Consequently, few neurons are generated, and the cortex ends up having a small size.
That is to say: thanks to the appearance of the gene MIR3607 the brain of mammalsincreased in size during evolutionand it still needs stem cells to keep it going for our brains to be their proper size.
Otherwise, cortical development and neurogenesis are deficient, leading to a much smaller size, just as occurred in rodents.
A finding that changes textbooks
This discovery helps us understand how evolutionary forces shaped our brain into what it is today. And also, how those same mechanisms have shaped the brain of other species, changing what the textbooks say.
The finding also has an impact at the clinical level, since the gene MIR3607 is now a potential genetic diagnostic marker for congenital brain malformations; in particular, those that affect brain size, such as microcephaly.
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*Victor Borrell Franco is CSIC Scientific Researcher, director of the Neurogenesis and Cortical Expansion group, Miguel Hernández University. This article was originally published on The Conversation and is published here under a Creative Commons license.
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