Scientists have developed primate brains on an unprecedented scale


We're not sure why it happened. Even when & # 39; is a topic of continuous debate. But at some point, for some reason, our brain got big.

There are many hypotheses about how we got here, but to find evidence, we need experiments with chimpanzee and human brains that involve practical (not to mention ethical) challenges. So these scientists went and built their own specimens.

"It's a science fiction experiment that could not have happened ten years ago," says cellular biologist Arnold Kriegstein of the University of California, San Francisco.

The team built simple, biochemically active brains from chimpanzees and human stem cells and used them to identify hundreds of genetic differences that could help explain their unique characteristics.

We're not just talking one or two here too. The researchers took cells from eight chimpanzees and ten humans and used them to generate a population of 56 specimens, providing an unprecedented scope for accurate measurements.

Technically, the brains of humans and chimpanzees that they have developed in laboratory glassware are not the fully developed pieces of wrinkled gray matter that you would find inside the skull of a primate.

They are organoids – blends of tissues that self-organized into a 3D structure to serve as a model for an organ.

Although the line between a real organ and its organoid derivative is confusing, it is clear that these neurological tissue cultures can not process information like the real one. But that is not the goal.

There is sufficient genetic and biochemical activity in these cultures to allow experiments that would be impossible on good faith specimens.

Extracting DNA and proteins from brains taken from dead chimpanzees and humans and keeping them side by side is like comparing the final credits of two films. You may know the actors, but you're missing the plots.

Brain organoids allow researchers to measure how genes activate and biochemistry floats, and the timing of the development of important cells and other structures.

Having dozens of organoids to compare means changes that are general to each species and can be chosen accurately.

The researchers deconstructed their specimens at different stages of development, allowing them to compare the types of emerging cells and the genetic programs being activated at each stage.

All were compared to reference materials taken from a third group of primates, rhesus macaques.

Contrasts in the genetic activity of human organoids and chimpanzees provide a fertile basis for identifying important mutations in each species that could explain how our respective brains evolved.

"These chimpanzee organoids give us a window that is inaccessible to six million years of our evolution," says neurologist Alex Pollen.

The analysis revealed 261 human-specific changes in gene expression; One particular change that caught their eye was a kind of neural precursor.

Several years ago, Kriegstein's laboratory identified the molecular characteristics of a type of cell that gives rise to most of the human cortical neurons, called the external radial glial cell. This time the team showed how the activity in these cells increased their participation in a path of growth in humans, highlighting a crucial change that may help explain the ramification of human evolution away from our great monkey relatives.

"Being so close to wild chimpanzees made me want to ask questions about the evolution of our own species," says Pollen, who studied the evolution of fish near the famous chimpanzee research facility in Gombe National Park.

"But we first need genomes, stem cells and single-stranded RNA sequencing to understand the evolutionary programs that drive brain development in both species."

Whatever the story is behind the unusually enlarged brains of humans and their fellow humans, it will be complex. Organoids provide new ways to study this activity on an unprecedented scale, laying the groundwork to show how small changes in our evolutionary past have led to major differences in our biology.

This research was published in Cell.


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