Lab-grown ‘minibrains’ are revealing what makes humans special

Ann Gibbons in Science:

Ever since Alex Pollen was a boy talking with his neuroscientist father, he wanted to know how evolution made the human brain so special. Our brains are bigger, relative to body size, than other animals', but it's not just size that matters. "Elephants and whales have bigger brains," notes Pollen, now a neuroscientist himself at the University of California, San Francisco. Comparing anatomy or even genomes of humans and other animals reveals little about the genetic and developmental changes that sent our brains down such a different path. Geneticists have identified a few key differences in the genes of humans and apes, such as a version of the gene FOXP2 that allows humans to form words. But specifically how human variants of such genes shape our brain in development—and how they drove its evolution—have remained largely mysterious. "We've been a bit frustrated working so many years with the traditional tools," says neurogeneticist Simon Fisher, director of the Max Planck Institute for Psycholinguistics in Nijmegen, the Netherlands, who studies FOXP2.

Now, researchers are deploying new tools to understand the molecular mechanisms behind the unique features of our brain. At a symposium at The American Society of Human Genetics here last month, they reported zooming in on the genes expressed in a single brain cell, as well as panning out to understand how genes foster connections among far-flung brain regions. Pollen and others also are experimenting with brain "organoids," tiny structured blobs of lab-grown tissue, to detail the molecular mechanisms that govern the folding and growth of the embryonic human brain. "We used to be just limited to looking at sequence data and cataloging differences from other primates," says Fisher, who helped organize the session. "Now, we have these exciting new tools that are helping us to understand which genes are important." Most of the talks focused on the development of the cerebral cortex, the wrinkled outer layer of the brain that orchestrates higher cognitive functions such as memory, attention, awareness, language, and thought. The human cortex is special, with three times as many cells as that of chimps, and deeper folds that help pack in those extra cells. These differences begin to unfold in the earliest phase of fetal development, but researchers know little about the genes that direct this transformation and the molecules they encode.

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