Symmetry breaking in development and stochastic gene expression

Abstract

The prevailing emphasis in developmental biology since the expansion of the molecular biology age has been that developmental decisions are instructive. A cell differentiates to become a specific cell type because it receives a signal, whereas its neighbor that does not receive the signal adopts a different fate. This emphasis has been generally accepted, largely because of the success of this view in tractable invertebrate model organisms, and the widespread similarities in molecular regulation to the development of more complex species. An alternative emphasis, that cells make their own decisions, has until the past decade been conspicuously silent. Here I trace the re-emergence of our appreciation of single cell decision-making in development, and how widespread this phenomenon is likely to be. I will focus the discussion on the potential role of stochastic gene expression in generating differences between cells in the absence of simple instructive signals and highlight the complexity of systems proposed to involve this type of regulation. Finally, I will discuss the approaches required to fully test hypotheses that noisy gene regulation can be extrapolated through developmental time to accurately specify cell fate. WIREs Dev Biol 2017, 6:e284. doi: 10.1002/wdev.284 For further resources related to this article, please visit the WIREs website.

Transition state dynamics during a stochastic fate choice

“…Decision-making based upon multiple small influences may be an emerging theme in developmental self-organisation, which likely extends well beyond Dictyostelium (Cannon et al, 2015;Chubb, 2017). Our data provide some clues as to what these influences are, most clearly the heterogeneity in the expression of cell cycle components in the initial pool of cells entering the mound.…”

Modulation of tissue growth heterogeneity by responses to mechanical stress

“…For instance, cell growth was found to be spatially heterogeneous (5)(6)(7)(8)(9), cell cycle length may appear random (10), and there is extensive evidence of stochastic gene expression (11,12). Such variability has been hypothesized to be required for the emergence of complex shapes since it favors symmetry breaking (13) and self-organization (14) during development. Nevertheless, growth variability would need to be restrained to ensure robust morphogenesis.…”

Modulation of tissue growth heterogeneity by responses to mechanical stress

“…For instance, cell growth was found to be spatially heterogeneous (5)(6)(7)(8)(9), cell cycle length may appear random (10), and there is extensive evidence of stochastic gene expression (11,12). Such variability has been hypothesised to be required for the emergence of complex shapes since it favors symmetry breaking (13) and self-organisation (14) during development. Nevertheless, growth variability would need to be restrained to ensure robust morphogenesis.…”