Rough maps outlining the development of the brain in humans and other mammals have shed light on susceptibility to neurodevelopmental and psychiatric disorders and establish new strategies for treatment.
The draft reference atlases, created by a global consortium of researchers, show how different brain cells are established in different species through neurodevelopment.
Outlined in a collection of Nature research papers, they highlight how the expression of genes and identity of cells changes dynamically through development and the cellular processes involved in the creation of different brain cell types.
The findings reveal time windows when the genetic risks for some psychiatric disorders are concentrated in ways that may improve understanding over how the disruption to critical genes during development can lead to conditions such as autism and schizophrenia.
The research could also help create targeted therapies and improve the way brain organoids and animal models are created for research.
“This set of work gives us a detailed blueprint of how different brain cell types emerge and mature over time,” said one of the researchers Hongkui Zeng, PhD, director of the Allen Institute for Brain Science in Seattle.
“By understanding when and where critical genes are turned on during development, we can begin to uncover how disruptions in that process may lead to disorders like autism or schizophrenia. It’s foundational knowledge that opens the door to better diagnoses and targeted treatments.”
The project began in 2022 from through the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) initiative from the U.S. National Institutes of Health.
The BRAIN Initiative Cell Atlas Network (BICAN) set out with the aim to build reference library of brain-cell types across several species.
The BICAN researchers used cutting-edge genetic and computer tools to examine how developmental timing interacted with how the identity of different brain cells was created, pinpointing timepoints where vulnerability to disease could arise.
While the identity of cells is particularly flexible during development, this can also lead to windows of susceptibility.
The researchers tracked how stem cells specialized into neurons and glial cells, tracing how gene activity was regulated and found that cell types emerged in overlapping waves rather than fixed stages. They also found that some developmental processes could be reactivated in adults or in disease situations.
Several studies examined inhibitory interneurons, which are a main class of brain cell that dampen the excitability of other neurons in the central nervous system. Others examined the means by which gene activity was coordinated, for example mapping the accessibility of chromatin to the cellular machinery that transcribes RNA.
Yet other studies examined how environment, such as parenting, social interactions, and sensory experiences, affected the paths of development.
Key findings included how human progenitor cells may be linked to glioblastoma brain cancer, and where time windows in which genetic risks for psychiatric disorders are concentrated.
“Together, this collection from the BICAN turns the static portrait of cell types into a dynamic story of the developing brain,” commented Emily Sylwestrak, PhD, from the University of Oregon, in an accompanying News&Views article.
“These data lay the groundwork for future studies to identify which developmental windows and transcriptional profiles are causal for the assembly and function of neuronal circuits, and for susceptibility to disease.”
