Single-cell imaging of the cell cycle reveals CDC25B-induced heterogeneity of G1 phase length in neural progenitor cells

Author:

Molina Angie1,Bonnet Frédéric1ORCID,Pignolet Julie1,Lobjois Valerie1ORCID,Bel-Vialar Sophie1,Gautrais Jacques2ORCID,Pituello Fabienne1ORCID,Agius Eric1ORCID

Affiliation:

1. Centre de Biologie Intégrative (CBI), Université de Toulouse, CNRS, Université Toulouse III – Paul Sabatier 1 Unité de Biologie Moléculaire, Cellulaire et du Développement (MCD) , , Toulouse 31062 CEDEX 9 , France

2. Centre de Recherches sur la Cognition Animale (CRCA), Centre de Biologie Intégrative (CBI), Université de Toulouse, CNRS, Université Toulouse III – Paul Sabatier 2 , Toulouse 31062 CEDEX 9 , France

Abstract

ABSTRACT Although lengthening of the cell cycle and G1 phase is a generic feature of tissue maturation during development, the underlying mechanism remains poorly understood. Here, we develop a time-lapse imaging strategy to measure the four cell cycle phases in single chick neural progenitor cells in their endogenous environment. We show that neural progenitors are widely heterogeneous with respect to cell cycle length. This variability in duration is distributed over all phases of the cell cycle, with the G1 phase contributing the most. Within one cell cycle, each phase duration appears stochastic and independent except for a correlation between S and M phase duration. Lineage analysis indicates that the majority of daughter cells may have a longer G1 phase than mother cells, suggesting that, at each cell cycle, a mechanism lengthens the G1 phase. We identify that the CDC25B phosphatase known to regulate the G2/M transition indirectly increases the duration of the G1 phase, partly through delaying passage through the restriction point. We propose that CDC25B increases the heterogeneity of G1 phase length, revealing a previously undescribed mechanism of G1 lengthening that is associated with tissue development.

Funder

Centre National de la Recherche Scientifique

Université Toulouse III - Paul Sabatier

Ministère de l'Enseignement Supérieur et de la Recherche

Agence Nationale de la Recherche

Fondation ARC pour la Recherche sur le Cancer

Université Fédérale Toulouse Midi-Pyrénées

Publisher

The Company of Biologists

Subject

Developmental Biology,Molecular Biology

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