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

3 Citations (Scopus)

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

Fingerprint

Neurons
Cell Cycle
Tubulin Modulators
Calcium
G2 Phase
Gene Expression Profiling
Dendrites
Cell Cycle Checkpoints
Cell Division
Cerebral Cortex
Genes
Axons
Up-Regulation
Gene Expression
Neoplasms

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

De Anda, F. C., Madabhushi, R., Rei, D., Meng, J., Gräff, J., Durak, O., ... 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

Cortical neurons gradually attain a post-mitotic state. / De Anda, Froylan Calderon; Madabhushi, Ram; Rei, Damien; Meng, Jia; Gräff, Johannes; Durak, Omer; Meletis, Konstantinos; Richter, Melanie; Schwanke, Birgit; Mungenast, Alison; Tsai, Li Huei.

In: Cell Research, Vol. 26, No. 9, 01.09.2016, p. 1033-1047.

Research output: Contribution to journalArticle

De Anda, FC, Madabhushi, R, Rei, D, Meng, J, Gräff, J, Durak, O, Meletis, K, Richter, M, Schwanke, B, Mungenast, A & Tsai, LH 2016, 'Cortical neurons gradually attain a post-mitotic state', Cell Research, vol. 26, no. 9, pp. 1033-1047. https://doi.org/10.1038/cr.2016.76
De Anda FC, Madabhushi R, Rei D, Meng J, Gräff J, Durak O et al. Cortical neurons gradually attain a post-mitotic state. Cell Research. 2016 Sep 1;26(9):1033-1047. https://doi.org/10.1038/cr.2016.76
De Anda, Froylan Calderon ; Madabhushi, Ram ; Rei, Damien ; Meng, Jia ; Gräff, Johannes ; Durak, Omer ; Meletis, Konstantinos ; Richter, Melanie ; Schwanke, Birgit ; Mungenast, Alison ; Tsai, Li Huei. / Cortical neurons gradually attain a post-mitotic state. In: Cell Research. 2016 ; Vol. 26, No. 9. pp. 1033-1047.
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