University of Virginia School of Medicine researchers have revealed how errors in the final stage of cell division can affect developing brain cells and may contribute to cancer and neurodevelopmental disorders. The final step of cell division, known as abscission, cuts the thin bridge connecting two daughter cells. Genes controlling this process have previously been linked to cancer and developmental conditions, but the consequences of abscission failure in the developing brain were not fully understood.
Noelle D. Dwyer and her team, led by graduate researcher Kaela S. Lettieri, studied these errors in the developing brains of mice. When cells failed to complete abscission, they merged back into enlarged cells containing two nuclei. Their outer membranes became larger, while the cilia that help cells receive signals became longer. Some cells also developed two cilia. The researchers found that the p53 protein normally protects the developing brain by identifying these abnormal cells and triggering their death. When the team blocked p53, the cells survived and attempted to divide again. These further divisions also failed, producing increasingly abnormal cells with multiple nuclei and cilia and disrupting the regular arrangement of the developing tissue.
The findings suggest that repeated cell-division errors may contribute to tumour formation and developmental disorders when protective mechanisms fail. The researchers believe that understanding how the developing brain maintains tight control over cell division could eventually support new approaches to preventing or treating certain cancers and birth defects.
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