Cortical neurons gradually attain a post-mitotic state

Froylan Calderon De Anda, Ram Madabhushi, Damien Rei, Jia Meng, Johannes Gräff, Omer Durak, Konstantinos Meletis, Melanie Richter, Birgit Schwanke, Alison Mungenast, Li Huei Tsai

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Once generated, neurons are thought to permanently exit the cell cycle and become irreversibly differentiated. However, neither the precise point at which this post-mitotic state is attained nor the extent of its irreversibility is clearly defined. Here we report that newly born neurons from the upper layers of the mouse cortex, despite initiating axon and dendrite elongation, continue to drive gene expression from the neural progenitor tubulin α1 promoter (Tα1p). These observations suggest an ambiguous post-mitotic neuronal state. Whole transcriptome analysis of sorted upper cortical neurons further revealed that neurons continue to express genes related to cell cycle progression long after mitotic exit until at least post-natal day 3 (P3). These genes are however down-regulated thereafter, associated with a concomitant up-regulation of tumor suppressors at P5. Interestingly, newly born neurons located in the cortical plate (CP) at embryonic day 18-19 (E18-E19) and P3 challenged with calcium influx are found in S/G2/M phases of the cell cycle, and still able to undergo division at E18-E19 but not at P3. At P5 however, calcium influx becomes neurotoxic and leads instead to neuronal loss. Our data delineate an unexpected flexibility of cell cycle control in early born neurons, and describe how neurons transit to a post-mitotic state.

Original languageEnglish (US)
Pages (from-to)1033-1047
Number of pages15
JournalCell Research
Volume26
Issue number9
DOIs
StatePublished - Sep 1 2016

Keywords

  • RNA-seq
  • calcium influx
  • cell cycle
  • channel rhodopsin
  • ionomycin
  • post-mitotic neuronal state

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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  • Cite this

    De Anda, F. C., Madabhushi, R., Rei, D., Meng, J., Gräff, J., Durak, O., Meletis, K., Richter, M., Schwanke, B., Mungenast, A., & Tsai, L. H. (2016). Cortical neurons gradually attain a post-mitotic state. Cell Research, 26(9), 1033-1047. https://doi.org/10.1038/cr.2016.76