Cell cycle regulation of oscillations yields coupling of growth and form in a computational model of the presomitic mesoderm

Abstract

A striking example of coupling between growth and form occurs during the segmentation of the vertebrate embryo. During segmentation, pairs of segments, one on either side of the anterior-posterior axis, bud off from the presomitic mesoderm (PSM) at regular intervals in time. In the clock and wavefront model, a multicellular oscillator regulates the time at which the next pair of segments form whilst a wavefront regulates their spatial location. In most mathematical models of segmentation, it is assumed that cells in the PSM are oscillators that have a constant natural frequency. Based on recent experimental findings, here we propose a model in which the natural oscillation frequency of each PSM cell is a function of its position in the cell cycle. Given adequate oscillator coupling and that cells in the PSM are randomly distributed in the cell cycle, we find that the emergent oscillator frequency is a weighted average of the constituent oscillator frequencies with the weightings dependent on the fraction of cells in a given cell cycle state. Here, we show that such a model can allow for coupling between pattern formation and growth rate in PSM tissue.

Keywords: Cell cycle; Clock and wavefront model; Coupled oscillator; NICD; Presomitic mesoderm; Somitogenesis clock.