LEM-3/ANKLE1 nuclease prevents the formation of abnormal syncytium to safeguard neuronal differentiation

In animal development, cells exit the cell cycle after a final round of cell division to differentiate into specialized cell types. However, the impact of failed cytokinesis on the fate specification of postmitotic cells, especially neurons, remains poorly understood. We analyzed the Caenorhabditis elegans mutants lacking the midbody-tethered endonuclease LEM-3/ANKLE1, which resolves chromatin bridges during cytokinesis. Using genetic analysis, fluorescence microscopy, and RNA visualization, we found that unresolved DNA bridges lead to the formation of stable intercellular bridges, creating binucleate syncytia between touch receptor neurons and sister cells, which allows thorough cytoplasmic mixing despite independent nuclear transcription. In some cases, the cytoplasmic linkage between sister cells also led to the suppression of neuronal fates and prevention of apoptotic fates. Thus, LEM-3 prevents syncytium formation to ensure proper cellular differentiation.