If a body is going to function correctly, the cells need to be in the right place. Scientists have learned a lot about how cell migration occurs during development, but the growth of the human brain is still a process we don't know a lot about. Every minute, about 250,000 neurons migrate as the fetal brain develops during a pregnancy. Many of those neurons move a long way from where they began. Researchers have been able to observe that process in animal models. Now, they've been able to study it in humans too, by assessing brain samples from healthy people who died of natural causes. The findings have been reported in Nature.
When a cell divides into daughter cells, a mutation or two might arise among the 3 billion base pairs in the genome, many of which are harmless. Those mutations can be tracked, to follow the trail left by a cell, which can then be read through DNA sequencing.
"By developing methods to read these mutations across the brain, we are able to reveal key insights into how the human brain forms, in comparison with other species," explained senior study author Joseph Gleeson, MD, the Rady Professor of Neuroscience at UC San Diego School of Medicine.
There are over 30 trillion cells in the human body, most of which contain the entire genome. Gleeson and colleagues have zeroed in on a relatively small number of genetic mutations that appear during early brain development. In this study, those few hundred mutations were tracked in deceased individuals, to reconstruct neural migration, and construct the first map of human brain development.
The researchers began by isolating various types of cells in the brain, and comparing the mutations present in those cell types. When the mutations in genomes of excitatory neurons were compared to mutations in inhibitory neurons, the comparison showed that these cells originated in different brain developmental zones, and later, they come together and mix in the cerebral cortex.
The study also showed that mutations in the left and right sides of the brain are not the same, which suggests that the hemispheres of the brain separate at an earlier developmental time point than we knew.
In certain human diseases such as intractable epilepsies, patients spontaneously have seizures, and surgery is necessary to remove epileptic foci, noted Martin W. Breuss, PhD, now an assistant professor at the University of Colorado School of Medicine.
The study authors also noted that the research explains why most foci tend to be exclusive to one side of the brain. The work may help scientists understand other neurological disorders too.