Abstract

The development of multicellular organisms proceeds through a series of morphogenetic and cell-state transitions, transforming homogeneous zygotes into complex adults by a process of self-organisation. Many of these transitions are achieved by spontaneous symmetry breaking mechanisms, allowing cells and tissues to acquire pattern and polarity by virtue of local interactions without an upstream supply of information. The combined work of theory and experiment has elucidated how these systems break symmetry during developmental transitions. Given that such transitions are multiple and their temporal ordering is crucial, an equally important question is how these developmental transitions are coordinated in time. Using a minimal mass-conserved substrate-depletion model for symmetry breaking as our case study, we elucidate mechanisms by which cells and tissues can couple reaction–diffusion-driven symmetry breaking to the timing of developmental transitions, arguing that the dependence of patterning mode on system size may be a generic principle by which developing organisms measure time. By analysing different regimes of our model, simulated on growing domains, we elaborate three distinct behaviours, allowing for clock-, timer- or switch-like dynamics. Relating these behaviours to experimentally documented case studies of developmental timing, we provide a minimal conceptual framework to interrogate how developing organisms coordinate developmental transitions.

Highlights

  • In developmental systems, it is important for the mechanistic constituents to “know” about the size of the living system as a whole [1,2]

  • We presented a minimal model for symmetry breaking to serve as a unifying framework to understand pattern formation in the context of timing and growth

  • We argue that systems that display positive feedback in activator recruitment, drawn from a limiting pool, can yield spontaneous symmetry breaking

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Summary

Introduction

It is important for the mechanistic constituents to “know” about the size of the living system as a whole [1,2]. While the mechanistic constituents and precise feedback architectures of RD mechanisms differ, many rely on a central motif of local activation and long-range inhibition [37] This concept has acted as an important heuristic in framing models of biological pattern formation, but importantly unifies diverse RD systems within a common mathematical framework. Many dynamical features of these models are applicable across systems and length scales In this perspective, we restrict our focus to RD models for biochemical pattern formation, elucidating the biological significance of a common dynamical feature shared across many motifs: the role of a critical system size for symmetry breaking [23,42,43]. We assumed a homogeneous P( x ) and a sinusoidal S( x ) profile of large wavelength

A Minimal Model for Size-Regulated Symmetry-Breaking
Size-Dependent Polarity Establishment in Budding Yeast
Neuronal Sequential Bipolarisation Coordinated by Membrane Growth
Regulating Pattern Size and Lifetime in Growing Systems
Case 1
Case 2
Case 3
20 L0 x transition x c α time x
Using Growth as a Timer
Overcoming Size Constraints
Autocatalysis as a Mechanism to Preserve Patterns in the Face of Growth
Discussion

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