An analysis of more than 2,300 nerve cells suggests that the developing human brain organizes itself before and after birth by removing large numbers of neurons that contain genetic abnormalities. The study found that more than one-quarter of neurons sampled from fetal brains had gained or lost portions of their chromosomes, compared with about 6% of neurons in the brains of babies after birth.
Published in Nature on October 28, the study1 indicates that many neurons with abnormal genomes are eliminated during development. “This suggests that the neurons that survived may be the ones that had the most intact genomes during development,” says Christos Proukakis, a neurologist at University College London who was not involved in the research.
Diane Hsiao, a pediatric neurogeneticist at Boston Children’s Hospital in Massachusetts and the paper’s lead author, says the findings reveal a previously unknown mechanism that helps regulate the number of neurons in the brain and determines which fetal neurons survive.
Understanding this process could help researchers investigate neurological conditions that commonly emerge during childhood, including autism spectrum disorder (ASD) and epilepsy.
A developmental quality-control system
Research in mice2 suggests that mammals eliminate many brain cells early in development through molecular programs that trigger cell death. Hsiao and her colleagues examined whether a similar process occurs in humans by studying brain tissue from deceased individuals ranging from fetuses as young as 14 weeks to people in their 90s.
The researchers focused on neurons in the cerebral cortex, the brain region involved in functions including memory, learning and consciousness. They sequenced the genomes of individual neurons to identify cells that had gained or lost sections of chromosomes, a phenomenon known as copy-number variation.
The analysis revealed a surprisingly large number of neurons with extensive copy-number variation during fetal development. The results were so unexpected that the researchers spent years determining whether they were genuine. The findings remained consistent when the team repeated the experiments using different single-cell sequencing methods.
After birth, however, the proportion of neurons with these abnormalities fell by more than fourfold, suggesting that many of the cells had been removed during development.
How are abnormal neurons identified?
It remains unclear how the brain distinguishes neurons with abnormal genomes from those that are suitable for survival. One possible clue is that neurons with high levels of copy-number variation tend to show abnormal activity in genes involved in forming connections, or synapses, with other neurons, Hsiao says.
Source: www.nature.com
