On the role of mechanical feedback in synchronous to asynchronous transition during embryogenesis

TL;DR

This paper develops a theoretical model to predict the critical cell cycle number at which zebrafish embryonic cells transition from synchronous to asynchronous division, highlighting biomechanical feedback as a key factor.

Contribution

It introduces a Gaussian-based cell cycle model predicting the SAT point and demonstrates biomechanical feedback's role in asynchronous growth emergence.

Findings

The model accurately predicts the SAT timing in zebrafish.

Biomechanical feedback influences cell division variability.

Fluctuations in cell cycle times increase linearly with divisions.

Abstract

Experiments have shown that during the initial stage of Zebrafish morphogenesis a synchronous to asynchronous transition (SAT) occurs, as the cells divide extremely rapidly. In the synchronous phase, the cells divide in unison unlike in the asynchronous phase. Despite the widespread observation of SAT in experiments, a theory to calculate the critical number of cell cycles, $n^{*}$, at which asynchronous growth emerges does not exist. Here, using a model for the cell cycle, with the assumption that cell division times are Gaussian distributed with broadening, we predict $n^{*}$ and the time at which the SAT occurs. The theoretical results are in excellent agreement with experiments. The theory, supplemented by agent based simulations, establish that the SAT emerges as a consequence of biomechanical feedback on cell division. The emergence of asynchronous phase is due to linearly increasing fluctuations in the cell cycle times with each round of cell division. We also make several testable predictions, which would further shed light on the role of biomechanical feedback on the growth of multicellular systems.