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

Abstract

While lengthening of the cell cycle and G1 phase is a generic feature of tissue maturation during development, the underlying mechanism remains still poorly understood. Here we develop a time lapse imaging strategy to measure the four cell cycle phases in single neural progenitor cells in their endogenous environment. We show that neural progenitors are widely heterogeneous regarding the cell cycle length. This duration variability is distributed over all phases of the cell cycle, with the G1 phase being the one 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 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 G2/M transition, indirectly increases the duration of the G1 phase partly through delaying restriction point crossing. We propose that CDC25B increases G1 phase range of heterogeneity revealing a novel mechanism of G1 lengthening associated with tissue development.

Downregulation of CDC25C in NPCs Disturbed Cortical Neurogenesis

“…Cdc25a knockdown ameliorates the high mitotic index of Microcephalin 1 ( Mcph1 )-deficient neuroprogenitors in vivo [ 28 ]. Single-cell imaging of the cell cycle reveals that CDC25B over-expression induced heterogeneity of G1 phase length in chick neural progenitor cells [ 29 ]. In addition, MCPH1 controls NPC entry into mitosis via the Chk1-Cdc25b centrosome maturation pathway [ 30 ].…”

R-loop and diseases: the cell cycle matters

“…The duration of the division phase accounts for a very small proportion of the whole cell cycle, and the overall time of the S, G2, and M phases is relatively constant. Therefore, the length of the cell cycle mainly depends on the G1 phase [3]. There is also a period in the cell cycle called the G0 phase in which cells are generally in a quiescent or dormant period.…”