In a package of 12 studies published in the Nature family of journals, researchers reveal new features of mammalian cell types during early development and begin to shed light on the environmental factors—including sensory inputs and social behavior—that affect how brains develop. The resulting comprehensive, cross-species developing brain cell atlases lay the foundation and provide powerful tools for a new era in the understanding of the human brain in health and disease.  

“It’s really been a long-standing mystery to understand how these processes occur,” said Tomasz Nowakowski, Ph.D., one of the study authors and associate professor of neurological surgery, anatomy, psychiatry and behavioral sciences at the University of California, San Francisco. “Building on the findings from the adult brain and venturing into the developmental stages is profoundly important because it is going to inform our understanding of the vulnerabilities and mutations which can lead to neurodevelopmental disorders.” 

This landmark achievement was supported by the National Institutes of Health’s Brain Research Through Advancing Innovative Neurotechnologies® Initiative, or The BRAIN Initiative®, aimed at accelerating the development of innovative neurotechnologies and revolutionizing our understanding of the human brain. 

“These maps are a phenomenal achievement, and very important references that are sorely needed as we seek to understand the mechanisms governing the developing brain in health and disease,” said Joshua Gordon, M.D./Ph.D., former director of the National Institute of Mental Health and current chair of Columbia University’s Department of Psychiatry. “They provide a scaffold on which we can construct a deeper understanding of autism, schizophrenia and other disorders that we know unfold during brain development.” 

Allen Institute scientists contributed three studies to this package. Transcriptomic and spatial organization of telencephalic GABAergic neurons focuses on a special group of brain cells in mice called GABAergic inhibitory neurons. These cells act like brakes in the brain, calming down excessive activity and helping different brain regions communicate smoothly. These neurons in humans are critical for everything we do, from movement and memory to managing emotions.  

Using data from over 1.2 million brain cells, the researchers created the most complete “family tree” of these cells to date, showing how they develop, spread out, and differentiate into distinct subtypes. One of the most striking findings shows how these cells travel long distances from where they are born to where they end up—sometimes crossing entire brain regions. Scientists also discovered that some of these neurons keep developing long after birth, especially in parts of the brain involved in learning, decision making, and emotions. This means there may be a longer window than previously thought for intervening and helping the brain rewire itself, particularly for children with developmental challenges. Researchers can now also identify which specific subtypes of GABAergic neurons are affected in different disorders and develop more targeted therapeutic approaches.