By the time a baby is born, their brain has lost a large number of neurons with genetic abnormalities.Credit: Getty
At the time of birth, the developing human brain mysteriously cleans itself by purging itself of large numbers of mutation-riddled neurons, according to a careful analysis of more than 2,300 nerve cells.
We are all mosaics: vast genetic diversity found between the cells of the same person
The analysis, published in Nature1 on October 28, found that more than a quarter of the neurons sampled in the brains of human fetuses had gained or lost several segments of their chromosomes. In contrast, only about 6% of neurons in babies’ brains after birth showed such abnormalities. “This suggests that the neurons that survive might be those that have retained the most intact genomes during development,” says Christos Proukakis, a neurologist at University College London, who was not involved in the study.
The findings reveal a new mechanism for regulating the number of neurons a person has and deciding which fetal neurons are allowed to persist in the brain, says Diane Shao, a pediatric neurogeneticist at Children’s Hospital Boston in Massachusetts and first author of the paper.
Knowing more about this process could be key to understanding neurological conditions that often appear during childhood, such as autism spectrum disorder (ASD) and epilepsy.
Quality control
Mouse studies2 suggested that, early in development, mammals eliminate many brain cells by activating a molecular program that leads to cell death. Shao and his colleagues analyzed human brain development by studying the brains of deceased individuals, ranging from fetuses at 14 weeks gestation to nonagenarians. The team focused on neurons in the cerebral cortex, a region of the brain responsible for, among other functions, memory, learning and consciousness.
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The team analyzed the genomes of individual neurons to look for those that had lost or gained certain chromosome segments, a phenomenon called copy number variation. The analysis revealed that a striking number of cells with extensive copy number variation were present during fetal development. There were so many that Shao and his colleagues spent years trying to determine whether the results were real. But even after repeating the experiment using a different single-cell sequencing method, the results were similar.
However, after birth, the proportion of these abnormal neurons was divided by four, suggesting that they were eliminated during development.
How does the brain know which neurons are normal and which are not? One possible clue, Shao says, is that brain cells with high levels of copy number variation also tend to show abnormal activity of genes involved in forming connections, or synapses, with other neurons.
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