LEM-3/ANKLE1 nuclease prevents the formation of abnormal syncytium to safeguard neuronal differentiation
- 1School of Biological Sciences, The University of Hong Kong, Hong Kong, Hong Kong SAR, China
Abstract
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.
Animal cells typically adopt their terminal identities during the final round of cell division, and so failed cytokinesis can strongly influence fate specification, especially in neurons. This study shows that the midbody-tethered endonuclease LEM-3 prevents syncytium formation to ensure proper cellular differentiation in C. elegans.
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BibTeX
@article{deng2026lem3ankle1,
title = {{LEM-3/ANKLE1 nuclease prevents the formation of abnormal syncytium to safeguard neuronal differentiation}},
author = {Siyu Deng and Chaogu Zheng},
journal = {PLOS Biology},
year = {2026},
month = nov,
doi = {10.1371/journal.pbio.3004099},
url = {https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3004099},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - LEM-3/ANKLE1 nuclease prevents the formation of abnormal syncytium to safeguard neuronal differentiation
AU - Siyu Deng
AU - Chaogu Zheng
PY - 2026
DA - 2026/11/02
JO - PLOS Biology
DO - 10.1371/journal.pbio.3004099
UR - https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3004099
AB - 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. Animal cells typically adopt their terminal identities during the final round of cell division, and so failed cytokinesis can strongly influence fate specification, especially in neurons. This study shows that the midbody-tethered endonuclease LEM-3 prevents syncytium formation to ensure proper cellular differentiation in C. elegans.
SN - 1545-7885
ER -