A meticulous reconstruction of how brain cells, both human and other mammals, develop and differentiate in the early stages of life.
An in-depth map of how the brain develops, stage by stage, in the embryonic phase and in the first weeks of life. A guide to understand which cells mature at a given moment, and from which progenitor cells: from now on, neuroscientists and geneticists who study the origin of some neurodevelopmental diseases will have it in their hands, thanks to the work of a US consortium of research groups called the Brain Initiative Cell Atlas Network (BICAN).
Five scientific articles recently published on Nature they chronicle the development and differentiation of hundreds of thousands of cells in the cerebral cortex of humans and mice, and analyze the molecular events that give rise to neurons and supporting cells, such as astrocytes. Overall, these works make up the most complete atlas ever created of how brain cells originate, a valuable tool for research into the origins of disorders that could have their roots in this phase of transformation, such as autism or schizophrenia.
Where it all began
The project was launched in 2022 by the BRAIN (Brain Research Through Advancing Innovative Neurotechnologies) initiative, coordinated by the US National Institutes of Health and financed with federal and private funds, which intends to “revolutionize our knowledge of the human brain”. The basic idea is to understand how the extremely differentiated and specialized cells that form the brain (human and other mammals) originate from stem cells.
«The objective of this research is to understand, for each cell, where it is formed, how it matures, where it is located and with which other cells it connects. Revolutionary techniques have been used such as spatial transcriptomics, which allows us to identify which genes are active at a given moment in each cell, maintaining information on the cell’s position within the tissue. In other words, not only which genes are active, but also where in the tissue their activation occurs” explains Marco Onorati, neurobiologist, associate professor of Cellular and Developmental Biology and head of the Neural Stem Cell Lab at the University of Pisa.
Subsequent generations
In one of five studies on Naturea group of neuroscientists from the University of California at San Francisco has reconstructed a “family tree” of the development of cells in the human brain cortex starting from brain tissues of fetuses at different stages of development.
The scientists identified over 6,400 progenitor cells in the samples and reconstructed which of them gave rise to the different types of brain cells. Up to 20 weeks of fetal development, the progenitor cells have favored the genesis of excitatory neurons, which stimulate other neurons with their signals; subsequently, the generation of inhibitory neurons prevailed, blocking neural communication.
The study also revealed that the production of brain support cells such as astrocytes, or cells that promote nerve signal transmission such as oligodendrocytes, is more continuous and prolonged in humans than in mice.
The first light
A group of scientists at the Allen Institute for Brain Science in Seattle, Washington, studied the development of cells in the visual cortex in the brains of mice, from when they were 11 and a half day old embryos to their 56th day of life. Discovering that some types of neurons continued to specialize well after birth, from when the mice opened their eyes for the first time, activating their visual apparatus, on the eleventh day of life, and up to the 21st day.
Therapeutic repercussions
Yet another study found that a subset of cells in a type of human malignant brain tumor (glioblastoma) are similar to embryonic progenitor cells, raising the possibility that this type of cancer somehow exploits cellular developmental processes to its advantage.
Overall, these types of studies will provide a compass for scientists investigating the neurobiological basis of some neurodevelopmental diseases, such as autism and schizophrenia. In fact, it will now be possible, as the authors of one of the studies write, “to sift through the data, to find genes that could be critical for a particular event in a particular type of cell and at a particular time”, to discriminate between genetic factors that make one vulnerable to brain pathologies and environmental factors, which make them visible.
“This massive collection of data from the BICAN consortium transforms the static portrait of neurons into a dynamic history of brain development with the potential to help understand the molecular causes of neurodevelopmental disorders. For many diseases of this type, today the diagnosis is reached when the processes that caused its manifestation have already been completed”, comments Antonio Uccelli, neurologist, full professor of Neurology at the University of Genoa, scientific director of the IRCCS Policlinico San Martino Hospital in Genoa and scientific coordinator of the Mnesys Project.
The human brain and others
The study will also allow us to compare some aspects of the evolution of the human brain with that of other mammals, and understand whether certain traits that we consider “unique” are, in fact, unique, or have instead been preserved during evolution also in other species of the group to which man belongs.
