A new study is the first to identify how human brains grow much larger, with three times as many neurons, compared with chimpanzee and gorilla brains.
From:
UK Research and Innovation
March 24, 2021 -- The study, led by researchers
at the Medical Research Council (MRC) Laboratory of Molecular Biology in
Cambridge, UK, identified a key molecular switch that can make ape brain
organoids grow more like human organoids, and vice versa.
The study, published in the
journal Cell, compared 'brain organoids' -- 3D tissues grown from
stem cells which model early brain development -- that were grown from human,
gorilla and chimpanzee stem cells.
Similar to actual brains, the human
brain organoids grew a lot larger than the organoids from other apes.
Dr Madeline Lancaster, from the MRC
Laboratory of Molecular Biology, who led the study, said: "This provides
some of the first insight into what is different about the developing human
brain that sets us apart from our closest living relatives, the other great
apes. The most striking difference between us and other apes is just how
incredibly big our brains are."
During the early stages of brain
development, neurons are made by stem cells called neural progenitors. These
progenitor cells initially have a cylindrical shape that makes it easy for them
to split into identical daughter cells with the same shape.
The more times the neural progenitor
cells multiply at this stage, the more neurons there will be later.
As the cells mature and slow their
multiplication, they elongate, forming a shape like a stretched ice-cream cone.
Previously, research in mice had shown
that their neural progenitor cells mature into a conical shape and slow their
multiplication within hours.
Now, brain organoids have allowed
researchers to uncover how this development happens in humans, gorillas and
chimpanzees.
They found that in gorillas and
chimpanzees this transition takes a long time, occurring over approximately
five days.
Human progenitors were even more delayed
in this transition, taking around seven days. The human progenitor cells
maintained their cylinder-like shape for longer than other apes and during this
time they split more frequently, producing more cells.
This difference in the speed of
transition from neural progenitors to neurons means that the human cells have
more time to multiply. This could be largely responsible for the approximately
three-fold greater number of neurons in human brains compared with gorilla or
chimpanzee brains.
Dr Lancaster said: "We have found
that a delayed change in the shape of cells in the early brain is enough to
change the course of development, helping determine the numbers of neurons that
are made.
"It's remarkable that a relatively
simple evolutionary change in cell shape could have major consequences in brain
evolution. I feel like we've really learnt something fundamental about the
questions I've been interested in for as long as I can remember -- what makes
us human."
To uncover the genetic mechanism driving
these differences, the researchers compared gene expression -- which genes are
turned on and off -- in the human brain organoids versus the other apes.
They identified differences in a gene
called 'ZEB2', which was turned on sooner in gorilla brain organoids than in
the human organoids.
To test the effects of the gene in
gorilla progenitor cells, they delayed the effects of ZEB2. This slowed the
maturation of the progenitor cells, making the gorilla brain organoids develop
more similarly to human -- slower and larger.
Conversely, turning on the ZEB2 gene
sooner in human progenitor cells promoted premature transition in human
organoids, so that they developed more like ape organoids.
The researchers note that organoids are
a model and, like all models, do not to fully replicate real brains, especially
mature brain function. But for fundamental questions about our evolution, these
brain tissues in a dish provide an unprecedented view into key stages of brain
development that would be impossible to study otherwise.
Dr Lancaster was part of the team that
created the first brain organoids in 2013.
https://www.sciencedaily.com/releases/2021/03/210324113502.htm
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