A blueprint for how to build a human brain

April 3, 2014

Reference atlas plate of the human fetal brain, color-coded by structure (credit: Allen Institute)

Researchers at the Allen Institute for Brain Science have generated a blueprint for how to build a human brain at unprecedented anatomical resolution.

This first major report using data from the  the BrainSpan Atlas of the Developing Human Brain is published in the journal Nature this week. The data provide insight into diseases like autism that are linked to early brain development, and to the origins of human uniqueness. The rich data set is publicly available via the Allen Brain Atlas data portal.

“Knowing where a gene is expressed in the brain can provide powerful clues about what its role is,” says Ed Lein, Investigator at the Allen Institute for Brain Science.  “This atlas gives a comprehensive view of which genes are on and off in which specific nuclei and cell types while the brain is developing during pregnancy. This means that we have a blueprint for human development: an understanding of the crucial pieces necessary for the brain to form in a normal, healthy way, and a powerful way to investigate what goes wrong in disease.”

This paper represents the first major report to make use of data collected for the BrainSpan Atlas of the Developing Human Brain, a science consortium initiative that seeks to create a map of the transcriptome across the entire course of human development.

“This atlas is already transforming the way scientists approach human brain development and neurodevelopmental disorders like autism and schizophrenia,” said Thomas R. Insel, Director of the National Institute of Mental Health.”

The researchers pointed to autism as a disorder with particularly pertinent links to early brain development. The research team used the BrainSpan Atlas to examine a number of genes linked to autism in prior scientific studies during development.

“We used the maps we created to find a hub of genetic action that could be linked to autism—and we found one,” says Lein. “These genes were associated with the newly generated excitatory neurons in the cortex, the area of the brain that is responsible for many of the cognitive features affected in autism such as social behavior. This discovery is an exciting example of the ability of the BrainSpan Atlas to generate meaningful hypotheses about the origins of brain developmental disorders.”

What makes humans unique?

Understanding what makes humans unique involves deciphering a complex puzzle—one that begins during the earliest phases of development. The richness of the BrainSpan Atlas gives scientists a new set of tools to assess how the human brain develops compared to other species.

“We know that some important regions of the genome show striking sequence differences in humans compared to other species,” says Lein. “Since where a gene is expressed in the brain can give insight into its function, we can use our map to begin to figure out the roles of those genes in making humans distinct. Our analysis of the data showed that these genes are enriched in the frontal cortex, as well as in several specific specialized cell types including inhibitory GABAergic interneurons and neurons of the transient subplate zone that serves as a scaffold during early circuit formation.  These features are all known to be expanded or show developmental differences in humans compared to other species, so our data gives unprecedented clues about the molecular underpinnings of what makes human neocortex unique.”

The BrainSpan Atlas enables researchers around the world to conduct research and ask questions about the early human brain that many would not be able to do otherwise, due to the highly limited availability of prenatal tissues.

The founding principal investigators in the consortium behind the BrainSpan project include Ed Lein and Michael Hawrylycz at the Allen Institute for Brain Science, Nenad Sestan and Mark Gerstein at Yale University, Jim Knowles at USC , Pat Levittat at The Saban Research Institute of Children’s Hospital Los Angeles and USC, Dan Geschwind at UCLA, and Bruce Fischl at Massachusetts General Hospital.