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.
Single-cell imaging of cell cycle reveals that tissue-scale g1 lengthening involves cdc25b induced cell-to-cell heterogeneity in neural progenitor cells
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Pluripotency of a founding field: rebranding developmental biology
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