The largest map of the developing brain reveals the phases in which neurological disorders originate

The human brain contains thousands of cell types that form through highly complex developmental processes. Understanding how these cells arise and organize has been a challenging task, as cell states change rapidly over time. Now, a series of twelve articles published in Nature by the international consortium BRAIN Initiative Cell Atlas Network (BICAN) offers the first dynamic and comparative portrait of the developing brain, from mouse to human.

Researchers have used single-cell technologies and space-based tools to track how stem cells transform into neurons and glial cells, how gene activity is regulated during development, and how sensory experiences and the environment influence the identity of brain cells. The results show that cell types do not appear in fixed phases, but rather in overlapping waves, and that some developmental programs can be reactivated in adulthood or in disease.

“These atlases offer a detailed blueprint of how different types of brain cells emerge and mature over time,” explains Hongkui Zeng, director of brain sciences at the Allen Institute and co-senior author. “By knowing when and where key genes are activated during development, we can begin to understand how disruptions in that process lead to disorders such as autism or schizophrenia.”

The studies, supported by the BRAIN Initiative of the US National Institutes of Health (NIH), also reveal that the diversification of neuronal types continues after birth, especially in GABAergic cells—which regulate brain activity—and in the visual cortex. In this region, new types of neurons form during key moments such as eye opening or early visual experiences, demonstrating that sensory influences shape brain development much more than previously thought.

As Zeng told SINC, “the most revealing finding has been the discovery that brain cells continue to change and diversify throughout the postnatal period.” In his view, this prolonged diversification “could underlie the brain’s ability to learn, adapt, and acquire new skills, but also make it more vulnerable to external influences and, at the same time, more capable of correcting dysfunctions.”

This prolongation of development, he adds, “forces us to rethink how we understand the causes of neuropsychiatric disorders: different disorders could involve subtle alterations in specific stages of this process, affecting certain types of cells or cellular mechanisms, which also opens up opportunities for intervention.”

Among the most outstanding discoveries of the Allen Institute team is the identification of a human progenitor cell that could be linked to glioblastoma —a type of brain cancer— and the location of time windows in which the genetic risks of psychiatric disorders are concentrated.

Comparing brain development across species, from mice to humans, has allowed researchers to identify both common traits and unique characteristics. However, “the most difficult aspect of studying or modeling the human brain is its prolonged postnatal development, which can last around 20 years, compared to 35 days in mice,” the researcher points out. “The human brain has a unique process of delayed maturation, called neoteny, which could be the basis for abilities such as language or intelligence, but precisely this duration makes it very difficult to capture experimentally.”

Looking ahead, the scientist tells SINC that the BICAN consortium aims to “create comprehensive maps of cell development throughout the animal brain, overlay available human data, and align results across species to fill critical gaps in our knowledge.”

The goal, he adds, “is to carry out large-scale computational analyses and simulations to understand the molecular forces that drive brain development and, from there, initiate functional studies that explain how sensation, behavior, and other brain functions arise over time.”

According to Zeng, this effort will have a triple impact: “First, we will better understand what makes the human brain unique. Second, we will be able to study more precisely when and where diseased brains change, both in human tissue and in animal models. And third, this knowledge will allow us to design better in vitro models and more precise gene- and cell-based therapies to treat neuropsychiatric diseases.”

The BICAN data collection is a fundamental resource for future studies seeking to link developmental stages with vulnerability to disease. It will also serve to improve the design of brain organoids and animal models, and to develop therapies targeting critical periods of development. Although there are still brain regions to study and challenges in integrating the data, researchers assert that these initial atlases are a decisive step toward a comprehensive understanding of the developing brain.