KYOTO — A study published in the journal Nature in June 2026 detailed the occurrence of DNA double-strand breaks in developing neurons. Researchers at Kyoto University's Institute for Integrated Cell-Material Sciences (WPI-iCeMS) led the study, finding these breaks are caused by mechanical stress during neuron migration and are subsequently repaired.

Newborn nerve cells migrate through dense tissue, past other cells, and between fibers to reach the brain cortex. The migration of these neurons through narrow spaces results in double-strand breaks in their DNA. Double-strand breaks involve the complete severing of both strands of the DNA double helix.

Professor Mineko Kengaku of WPI-iCeMS led the research. Researchers guided neurons through microchannels designed to replicate the narrow spaces found in developing brain tissue. Fluorescent markers showed DNA double-strand breaks formed as neurons passed through these microchannels, and these breaks disappeared after the neurons reached the other side.

Most DNA breaks in the migrating neurons were repaired within 24 hours. The repaired neurons showed no lasting effects on function. The DNA breaks are traced to the enzyme Topoisomerase IIβ, which normally makes controlled cuts in DNA to release torsional strain. Under mechanical stress, Topoisomerase IIβ becomes stuck mid-process, leaving broken ends of DNA.

The repair pathway known as non-homologous end joining stitches the broken DNA ends back together. In neurons, DNA damage occurs mainly in non-critical regions of the genome rather than in active genes. "The developing brain appears to have evolved to tolerate and repair the neuronal damage efficiently," Professor Kengaku said. "But understanding the limits of that tolerance-and what happens when repair is incomplete-brings us closer to understanding a range of neurological conditions."

Researchers engineered mice in which new neurons in the cerebellum lacked Ligase 4, an enzyme critical for repair. The engineered mice developed normally but gradually showed mild, progressive balance difficulties from early adulthood. These balance difficulties are reminiscent of human genome instability syndromes that affect the cerebellum. The study was a collaboration between Kyoto University, the University of Tokyo, the University of Osaka, the National University of Singapore, and the Tokyo Metropolitan Institute of Medical Science. The study is titled "Confined migration induces non-lethal DNA damage in developing neurons."

No independent assessment was available for this report.