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Primary neurons can enter M-phase

By Chaska C Walton, Wei Zhang, Iris Patiño-Parrado, Estíbaliz Barrio-Alonso, Juan-José Garrido, José M. Frade

Posted 25 Mar 2018
bioRxiv DOI: 10.1101/288589 (published 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.

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