During fetal development, the human brain produces an enormous surplus of neurons, only to destroy a substantial share of them shortly before and just after birth. Neuroscientists have long known about this phenomenon, but its purpose remained unclear. Now a joint study by Harvard Medical School and Boston Children's Hospital, published in the journal Nature, has shown that the process serves as a kind of quality control.
The scientists found that the fetal brain contains many cells with genetic defects, so-called copy number variations, in which large stretches of DNA are duplicated or, conversely, lost. Such changes have been linked to autism, schizophrenia and epilepsy. It turned out that up to 46% of neurons in the brain before birth carry such variations. After birth, however, their share drops sharply, to about 6%.
To understand the mechanism of this selection, the researchers analyzed the DNA and RNA of more than 44,000 individual cells of the cerebral cortex. They discovered that neurons with genetic defects cannot produce the proteins needed to form synapses, the connections with other neurons. In the developing brain, neurons literally compete for the right to integrate into the neural network. Those that successfully form connections receive signals that sustain their survival. Neurons that fail to do so trigger a program of cell death.
This struggle for survival, a Darwinian competition, turned out to be a natural quality-control mechanism in the brain.
— Christopher Walsh, one of the leaders of the study
According to Christopher Walsh, professor of pediatrics and neurology, the scientists were wholly unprepared for how widespread such mutations are at early stages of development. He compared this with observations in in vitro fertilization, where early embryos often contain cells with genetic abnormalities, yet healthy children ultimately develop from them.
The researchers believe that a failure in this selection system may explain why genetically vulnerable neurons persist and potentially lead to disorders of nervous system development. The team is now studying whether this mechanism is weakened in autism. Another line of work is to determine whether defective neurons that escape destruction at birth may become more vulnerable in old age and accelerate the development of diseases such as Alzheimer's.
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