Fetal Brain Purges Mutation-Riddled Neurons Before Birth

More than one-quarter of neurons in the developing human fetal brain carry significant genetic abnormalities, but the vast majority of these “mutant” cells are purged by the time a baby is born. This biological cleanup, detailed in a study published in Nature, reveals that the brain eliminates a vast number of neurons riddled with mutations around the time of birth.

Researchers analyzed more than 2,300 nerve cells from the cerebral cortex—the area of the brain managing consciousness, learning, and memory—across a range of individuals from 14-week-old fetuses to people in their nineties. The team looked for copy number variation, which occurs when neurons gain or lose several segments of their chromosomes.

The Scale of Neural Purging

The analysis found a stark difference in genetic stability between fetal and postnatal brains. While more than 25% of sampled fetal neurons exhibited chromosomal abnormalities, that figure dropped to approximately 6% in the brains of babies after birth. This represents a more than fourfold decrease in the proportion of abnormal neurons.

Diane Shao, a paediatric neurogeneticist at Boston Children’s Hospital and the paper’s first author, stated that these findings uncover a new mechanism for deciding which fetal neurons persist and regulating the total number of neurons a person possesses. Christos Proukakis, a neurologist at University College London, noted that the data suggests the surviving neurons are likely those that maintained the most intact genomes during development.

Identifying Abnormal Cells

The research team spent years verifying the results due to the “stunning number” of cells with widespread copy number variation found during fetal development. The findings remained consistent even after the team repeated the experiment using a different single-cell sequencing method.

Shao suggested a possible clue as to how the brain identifies which cells to cull: neurons with high levels of copy number variation also tended to exhibit abnormal activity in genes responsible for forming synapses, or connections, with other neurons.

Clinical Implications

The study builds on previous research in mice suggesting mammals use a molecular program to eliminate many brain cells during early development. Researchers believe that gaining a deeper understanding of this human purging process could be essential for understanding epilepsy and autism spectrum disorder (ASD), conditions that frequently appear in childhood.

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