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A Comparative Approach for Quantitative Cell Counting Studies in Widely Different Mammalian Brains

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Published on: January 16, 2026

Cortical neurons gradually attain a post-mitotic state.

Froylan Calderon de Anda^1,2, Ram Madabhushi², Damien Rei²

¹Center for Molecular Neurobiology Hamburg (ZMNH), University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany.

|June 22, 2016

Summary

Newly generated neurons maintain cell cycle gene expression after exiting mitosis, indicating a flexible post-mitotic state. This flexibility diminishes as neurons mature, transitioning towards irreversible differentiation.

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Area of Science:

Neuroscience
Developmental Biology
Cell Biology

Background:

Neurons are traditionally considered terminally differentiated post-mitotic cells.
The exact timing and irreversibility of the post-mitotic state in neurons remain incompletely understood.

Purpose of the Study:

To investigate the cell cycle status and gene expression profiles of newly generated cortical neurons.
To define the transition period and flexibility of the post-mitotic state in developing neurons.

Main Methods:

Whole transcriptome analysis of sorted upper cortical neurons.
Assessment of cell cycle phase entry via calcium influx stimulation.
Analysis of gene expression related to cell cycle and tumor suppression.

Main Results:

Newly born upper cortical neurons express cell cycle genes post-mitotic exit until at least postnatal day 3 (P3).
Neurons at embryonic day 18-19 (E18-E19) and P3 can re-enter the cell cycle upon calcium stimulation, with division possible at E18-E19 but not P3.
Tumor suppressor gene expression increases by P5, coinciding with the downregulation of cell cycle genes.

Conclusions:

Early born neurons exhibit a flexible, ambiguous post-mitotic state with retained cell cycle potential.
This flexibility is transient, with neurons progressively committing to a terminally differentiated state.
Calcium influx transitions from promoting cell cycle entry to inducing neurotoxicity in later developmental stages.