That the neurons that survive may be the ones that have kept the most intact genomes during development,
notes Christos Proukakis, a neurologist at University College London.
Around the time of birth, the human brain purges vast numbers of mutation-riddled neurons, leaving behind cells with more intact genomes. Published October 28 in Nature, a new analysis of more than 2,300 nerve cells reveals this quality-control mechanism, which could shed light on childhood neurological conditions.
By the time a baby draws its first breath, its brain has quietly liquidated a staggering volume of cells bearing genetic abnormalities. A painstaking single-cell analysis published in Nature on October 28 uncovers that human brains undergo a massive developmental clean-up around the time of birth, clearing out neurons riddled with mutations.
The study examined more than 2,300 individual nerve cells and discovered that over one-quarter of neurons sampled from human fetuses had either gained or lost multiple segments of their chromosomes. In stark contrast, only about 6% of neurons from babies after birth carried similar chromosomal abnormalities. Christos Proukakis, a neurologist at University College London who was not involved in the research, noted that the data points toward survival of the fittest for our neural wiring, suggesting that the neurons that survive may be the ones that have kept the most intact genomes during development.
Mapping the Cerebral Cortex at Single-Cell Resolution
To understand how human brains develop structurally, the research team studied brain tissue from deceased individuals ranging from fetuses at 14 weeks of gestation all the way to nonagenarians. Investigators concentrated specifically on neurons within the cerebral cortex, the critical brain region that governs consciousness, learning, and memory.
Verifying Unexpected Genomic Anomalies
The team tracked copy number variation—a phenomenon where cells have gained or lost specific chromosomal segments. Fetal brain tissue revealed such an extraordinary abundance of these abnormal cells that lead author Diane Shao, a paediatric neurogeneticist at Boston Children’s Hospital in Massachusetts, and her colleagues spent years verifying whether the results were genuine. Even after running the experiments again through an alternative single-cell sequencing method, the findings held firm.
A Steep Postnatal Drop in Mutation-Laden Cells
Once past birth, however, the proportion of these mutation-laden neurons dropped by more than fourfold. This indicates that the developing brain actively culls these anomalous cells during development, establishing a newly revealed biological check on how many neurons ultimately persist.
Implications for Epilepsy and Autism Spectrum Disorder
While earlier studies in mice pointed to mammalian brain cells dying off during early development via an activated molecular program, the new human-focused findings open fresh avenues for investigating neurodevelopmental conditions. Shao explains that deciphering this elimination process could prove essential for understanding childhood-onset neurological disorders, including epilepsy and autism spectrum disorder.
Unresolved Questions in Synaptic Gene Activity
The mechanism by which the developing brain flags and destroys these flawed cells remains an active puzzle. As researchers probe deeper into the timeline of cellular selection, a potential indicator has emerged from the data: brain cells possessing high levels of copy number variation also displayed erratic activity in genes responsible for building synapses, the vital connections linking neurons together.
