Abstract
ABSTRACTIn development and disease, cells move as they exchange signals. One example is found in vertebrate development, during which the timing of segment formation is set by a ‘segmentation clock’, in which oscillating gene expression is synchronized across a population of cells by Delta-Notch signaling. Delta-Notch signaling requires local cell-cell contact, but in the zebrafish embryonic tailbud, oscillating cells move rapidly, exchanging neighbors. Previous theoretical studies proposed that this relative movement or cell mixing might alter signaling and thereby enhance synchronization. However, it remains unclear whether the mixing timescale in the tissue is in the right range for this effect, because a framework to reliably measure the mixing timescale and compare it with signaling timescale is lacking. Here, we develop such a framework using a quantitative description of cell mixing without the need for an external reference frame and constructing a physical model of cell movement based on the data. Numerical simulations show that mixing with experimentally observed statistics enhances synchronization of coupled phase oscillators, suggesting that mixing in the tailbud is fast enough to affect the coherence of rhythmic gene expression. Our approach will find general application in analyzing the relative movements of communicating cells during development and disease.
Highlights
Tissue organization in animal embryos involves relative cell movement
We develop a framework to analyze and model cell mixing quantitatively using zebrafish somitogenesis as a model system, and apply the framework to determine the impact of cell mixing on synchronization of genetic oscillators
The nuclei of cells in tailbud, presomitic mesoderm (PSM) and posterior somites in zebrafish embryos (n=4) were imaged with high temporal resolution for an interval corresponding to the formation of one somite, starting at the 15-17 somite stage, from a lateral orientation by confocal microscopy using a setup for multipleembryo time-lapse recording (Fig. 1A; Movie 1) (Bhavna et al, 2016)
Summary
Tissue organization in animal embryos involves relative cell movement. The importance of cell movement in development has been emphasized, for example in gastrulation, tissue elongation and neural development (Friedl and Gilmour, 2009; Rørth, 2009; Tada and Heisenberg, 2012). Many developmental processes involve cell movement and local intercellular signaling simultaneously, which means that the relative durations, or timescales, of these processes may play a role in successful communication. Cells modify their internal states due to received signals and the time taken for this determines a signaling timescale. When the mixing timescale is similar to, or faster than, the local signaling timescale, cells can exchange neighbors and start new local interactions before completing the internal state change due to previous signaling events, and movement can affect the flow of information across a tissue (Uriu et al, 2014). Little attention has been paid to the relation between the timescales of these two processes, or how cell mixing affects local intercellular interactions and the resulting tissue organization
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