Scientists have discovered how a critical protein acts as a guardian in the developing brain, destroying cells that make mistakes during division before they can turn into dangerous “monster” cells. The finding sheds new light on how cancer and neurodevelopmental disorders take hold, and may eventually point to ways to stop them before they start.
During cell division, the final step called abscission involves cutting the thin bridge that connects two new “daughter” cells. If that cut fails, the cells can merge back into one double-size cell. Normally, the body’s p53 protein detects these faulty cells and triggers their self-destruction. But when researchers blocked p53 in lab mice, the abnormal cells survived. They tried and failed to divide again, becoming giant cells with multiple nuclei and multiple hairlike cilia, disrupting the honeycomb pattern of the developing brain.
“When we first examined the tissue, the abnormal changes from cells that failed abscission were present, but more subtle, likely due to the abnormal cells undergoing cell death,” said Kaela S. Lettieri, a graduate student who led the study. “Therefore, when we blocked cell death and reexamined the tissue, it was striking to observe how much worse the abnormal cells became.” The researchers believe this multiplying mistake may be what drives tumor growth and developmental disorders.
The findings highlight p53 as a powerful safeguard for the growing brain. But the study also reveals what happens when that safeguard fails: the effects cascade over time, creating increasingly abnormal cells. “The developing brain seems to have specialized mechanisms of cell division to make billions of neurons in a short time window, and also a more sensitive p53 response than other organs,” said researcher Noelle D. Dwyer, PhD. “If we can figure out how our brains maintain such exquisite control of these processes, this could eventually help us devise treatments or prevention for all sorts of birth defects and cancers.”
The research team, which also included Katrina C. McNeely, published their findings in the journal Molecular Biology of the Cell. The work was supported by the National Institutes of Health and the UVA Brain Institute. By targeting the p53 pathway, researchers hope to one day create therapies that stop certain cancers early or prevent neurodevelopmental problems long before birth.