Researchers tracked the cellular migration of the developing fetal brain for the first time and also identified genetic mutations in the brains of deceased adults.
The formation of the human brain remains a largely unexplored process. It starts in the embryonic neural tube and progresses to over 100 billion interconnected neurons in the newborn brain. To reach this rate at human birth, the developing fetal brain must grow at an average rate of approximately 250,000 nerve cells per minute throughout pregnancy.
These nerve cells are often generated far from where they will eventually reside and function, and migration, although studied in animal models using chemical or biological indicators, has never been studied directly in humans.
Scientists at the University of California San Diego School of Medicine and the Ready Children's Institute for Genomic Medicine describe new methods for determining the movement of human brain cells during fetal development by examining the brains of healthy adults who have recently died of natural causes.
“Each time a cell divides into two daughter cells, one or more new mutations are randomly generated that leave a breadcrumb trail that can be read by modern DNA sequencers,” said senior author Joseph Gleason, MD. “By developing methods to read these mutations, we can unlock key insights into how the human brain is formed compared to other species.”
Gleason and his colleagues focused their efforts on just a few hundred mutations, which likely originated during the first few cell divisions after embryonic fertilization or early in brain development. By tracking these mutations throughout the brains of deceased people, they were able to reconstruct the development of the human brain for the first time.
To understand the breadcrumb cell type, scientists have developed methods to isolate each of the major cell types in the brain. For example, by profiling mutations in excitatory versus inhibitory neurons, they confirmed a long-standing suspicion that the two cell types originate in different germinal regions of the brain and then mix together in the cortex.
However, they also found that the mutations found in the left and right hemispheres of the brain are different from each other. This may suggest that the two hemispheres separate during development much earlier than previously thought.
"The results have implications for some human diseases, such as intractable epilepsy, where patients exhibit spontaneous seizures and require surgery to remove an epileptic focus in the brain," said Martin W. Breiss, assistant professor at the University of Colorado School of Medicine. According to the authors, this study will help to understand why lesions are almost always limited to one hemisphere of the brain.
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