Symmetry breaking in biology

Cells, 2020

Cellular morphogenesis is governed by the prepattern based on the symmetry-breaking emergence of dense protein clusters. Thus, a cluster of active GTPase Cdc42 marks the site of nascent bud in the baker's yeast. An important biological question is which mechanisms control the number of pattern maxima (spots) and, thus, the number of nascent cellular structures. Distinct flavors of theoretical models seem to suggest different predictions. While the classical Turing scenario leads to an array of stably coexisting multiple structures, mass-conserved models predict formation of a single spot that emerges via the greedy competition between the pattern maxima for the common molecular resources. Both the outcome and the kinetics of this competition are of significant biological importance but remained poorly explored. Recent theoretical analyses largely addressed these questions, but their results have not yet been fully appreciated by the broad biological community. Keeping mathematical apparatus and jargon to the minimum, we review the main conclusions of these analyses with their biological implications in mind. Focusing on the specific example of pattern formation by small GTPases, we speculate on the features of the patterning mechanisms that bypass competition and favor formation of multiple coexisting structures and contrast them with those of the mechanisms that harness competition to form unique cellular structures.

Developmental biology, 2014

Asymmetric development of the vertebrate embryo has fascinated embryologists for over a century. Much has been learned since the asymmetric Nodal signaling cascade in the left lateral plate mesoderm was detected, and began to be unraveled over the past decade or two. When and how symmetry is initially broken, however, has remained a matter of debate. Two essentially mutually exclusive models prevail. Cilia-driven leftward flow of extracellular fluids occurs in mammalian, fish and amphibian embryos. A great deal of experimental evidence indicates that this flow is indeed required for symmetry breaking. An alternative model has argued, however, that flow simply acts as an amplification step for early asymmetric cues generated by ion flux during the first cleavage divisions. In this review we critically evaluate the experimental basis of both models. Although a number of open questions persist, the available evidence is best compatible with flow-based symmetry breakage as the archetypi...

2003

Progress in Biophysics and Molecular Biology, 2019

Symmetry-based explanations using symmetry breaking (SB) as the key explanatory tool have complemented and replaced traditional causal explanations in various domains of physics. The process of spontaneous SB is now a mainstay of contemporary explanatory accounts of large chunks of condensed-matter physics, quantum field theory, nonlinear dynamics, cosmology, and other disciplines. A wide range of empirical research into various phenomena related to symmetries and SB across biological scales has accumulated as well. Led by these results, we identify and explain some common features of the emergence, propagation, and cascading of SB-induced layers across the biosphere. These features are predicated on the thermodynamic openness and intrinsic functional incompleteness of the systems at stake and have not been systematically analyzed from a general philosophical and methodological perspective. We also consider possible continuity of SB across the physical and biological world and discuss the connection between Darwinism and SB-based analysis of the biosphere and its history.

Phenomenology and the Cognitive Sciences, 2017

This article surveys and synthesizes dynamic systems models of development from biology, neuroscience, and psychology in order to propose an integrated account of growth, learning, and behavior. Key to this account is the concept of self-differentiation or symmetry-breaking. I argue that development can be understood as a cascade of symmetry-breaking events brought about by the ongoing interactions of multiple, nested, nonlinear dynamic systems whose self-organizing behaviors gradually alter their own anatomical conditions.

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PLoS biology, 2016

Cell migration in the "correct" direction is pivotal for many biological processes. Although most work is devoted to its molecular mechanisms, the cell's preference for one direction over others, thus overcoming intrinsic random motility, epitomizes a profound principle that underlies all complex systems: the choice of one axis, in structure or motion, from a uniform or symmetric set of options. Explaining directional motility by an external chemo-attractant gradient does not solve but only shifts the problem of causation: whence the gradient? A new study in PLOS Biology shows cell migration in a self-generated gradient, offering an opportunity to take a broader look at the old dualism of extrinsic instruction versus intrinsic symmetry-breaking in cell biology.

Mathematical modeling has been instrumental in identifying common principles of cell polarity across diverse systems. These principles include positive feedback loops that are required to destabilize a spatially uniform state of the cell. The conserved small G-protein Cdc42 is a master regulator of eukaryotic cellular polarization. Here we discuss recent developments in studies of Cdc42 polarization in budding and fission yeasts and demonstrate that models describing symmetry-breaking polarization can be classified into six minimal classes based on the structure of positive feedback loops that activate and localize Cdc42. Owing to their generic system-independent nature, these model classes are also likely to be relevant for the G-protein-based symmetry-breaking systems of higher eukaryotes. We review experimental evidence pro et contra different theoretically plausible models and conclude that several parallel and non-mutually exclusive mechanisms are likely involved in cellular polarization of yeasts. This potential redundancy needs to be taken into consideration when interpreting the results of recent cell-rewiring studies.

Proceedings of the International MultiConference of …, 2009

Abstract—We investigated the minimal condition for symmetry breaking in morphogenesis of cellular population using cellular automata based on reaction-diffusion dynamics. We started to understand the morphogenic process and provide the mathematical formulations of the ...

A computational theory and model of the ontogeny and development of bilateral symmetry in multicellular organisms is presented. Understanding the origin and evolution of bilateral organisms requires an understanding of how bilateral symmetry develops, starting from a single cell. Bilateral symmetric growth of a multicellular organism from a single starter cell is explained as resulting from the opposite handedness and orientation along one axis in two daughter founder cells that are in equivalent developmental control network states. Several methods of establishing the initial orientation of the daughter cells (including oriented cell division and cell signaling) are discussed. The orientation states of the daughter cells are epigenetically inherited by their progeny. This results in mirror development with the two founding daughter cells generating complementary mirror image multicellular morphologies. The end product is a bilateral symmetric organism. The theory gives a unified explanation of diverse phenomena including symmetry breaking, situs inversus, gynandromorphs, inside-out growth, bilaterally symmetric cancers, and the rapid, punctuated evolution of bilaterally symmetric organisms in the Cambrian Explosion. The theory is supported by experimental results on early embryonic development. The theory makes precise testable predications.