Neuroscientists Just Launched an Atlas of the Developing Human Brain

Your brain is one enigmatic hunk of meat—a wildly complex web of neurons numbering in the tens of billions. But years ago, when you were in the womb, it began as little more than a scattering of undifferentiated stem cells. A series of genetic signals transformed those blank slates into the wrinkly, three-pound mass between your ears. Scientists think the way your brain looks and functions can be traced back to those first molecular marching orders—but precisely when and where these genetic signals occur has been difficult to pin down.

Today, things are looking a little less mysterious. A team of researchers led by neuroscientists at UC San Francisco has spent the last five years compiling the first entries in what they hope will become an extensive atlas of gene expression in the developing human brain. The researchers describe the project in the latest issue of Science, and, with the help of researchers at UC Santa Cruz, they’ve made an interactive version of the atlas freely available online.

“The point of creating an atlas like this is to understand how we make a human brain,” says study coauthor Aparna Bhaduri. To do that, she and her colleagues analyzed not only how gene expression varies from cell to cell, but where and at what stages of brain development those genes come into play.

Crucially, the researchers performed that analysis at the level of individual brain cells—a degree of specificity neuroscientists have struggled to achieve in the past. That’s huge, in part because it gives researchers their clearest picture yet of where and in which cells certain genes are expressed in the fetal brain. But it also means scientists can begin to characterize early brain cells not according to things like their shape and location (two variables that neuroscientists have long used to classify cellular types and subtypes), but by the bits of DNA they turn on and off. As developmental neurobiologist Ed Lein, who was unaffiliated with the study, says: “This is not the first study in this area by any means, but the single cell technique is a game changer.”

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Lein would know. An investigator at the Allen Institute for Brain Science (a key institutional player in the mission to map the human brain, and the home of several ambitious brain atlas projects from the past decade), he and his colleagues performed a similar survey of gene expression in developing human brains in 2014. To build it, they sliced fetal brain tissue into tiny pieces and scanned them for gene expression. But even after dissecting them as finely as possible, Lein says the cell populations of the resulting brain bits were still extremely diverse. Even a microscopic speck of gray matter contains a menagerie of functionally distinct cells, from astrocytes to neurons to microglia (though, to be perfectly frank, neuroscientists aren’t even sure how many cell types exist).

“When we measured the genes in our samples,” says Lein, “what we actually saw was the average output of all the cells in that sample.” When they were through, Lein and his colleagues had mapped the location and activity of some 20,000 genes in anatomical regions throughout the brain. But they still didn’t know which individual cells those genes came from.

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