Primary neurons can enter M-phase

Sci Rep. 2019 Mar 14;9(1):4594. doi: 10.1038/s41598-019-40462-4.


Differentiated neurons can undergo cell cycle re-entry during pathological conditions, but it remains largely accepted that M-phase is prohibited in these cells. Here we show that primary neurons at post-synaptogenesis stages of development can enter M-phase. We induced cell cycle re-entry by overexpressing a truncated Cyclin E isoform fused to Cdk2. Cyclin E/Cdk2 expression elicits canonical cell cycle checkpoints, which arrest cell cycle progression and trigger apoptosis. As in mitotic cells, checkpoint abrogation enables cell cycle progression through S and G2-phases into M-phase. Although most neurons enter M-phase, only a small subset undergo cell division. Alternatively, neurons can exit M-phase without cell division and recover the axon initial segment, a structural determinant of neuronal viability. We conclude that neurons and mitotic cells share S, G2 and M-phase regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Differentiation
  • Cell Division*
  • Cyclin E / genetics
  • Cyclin E / metabolism
  • Cyclin-Dependent Kinase 2 / genetics
  • Cyclin-Dependent Kinase 2 / metabolism
  • Cytokinesis
  • G2 Phase
  • Humans
  • Neurons / metabolism*
  • Oncogene Proteins / genetics
  • Oncogene Proteins / metabolism
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism


  • CCNE1 protein, human
  • Cell Cycle Proteins
  • Cyclin E
  • Oncogene Proteins
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Protein-Tyrosine Kinases
  • WEE1 protein, human
  • CDK2 protein, human
  • Cyclin-Dependent Kinase 2