Cytoskeletal Symmetry Breaking and Chirality: From Reconstituted Systems to Animal Development

Abstract

Animal development relies on repeated symmetry breaking, e.g., during axial specification, gastrulation, nervous system lateralization, lumen formation, or organ coiling. It is crucial that asymmetry increases during these processes, since this will generate higher morphological and functional specialization. On one hand, cue-dependent symmetry breaking is used during these processes which is the consequence of developmental signaling. On the other hand, cells isolated from developing animals also undergo symmetry breaking in the absence of signaling cues. These spontaneously arising asymmetries are not well understood. However, an ever growing body of evidence suggests that these asymmetries can originate from spontaneous symmetry breaking and self-organization of molecular assemblies into polarized entities on mesoscopic scales. Recent discoveries will be highlighted and it will be discussed how actomyosin and microtubule networks serve as common biomechanical systems with inherent abilities to drive spontaneous symmetry breaking.

Planar cell polarity in the C. elegans embryo emerges by differential retention of aPARs at cell-cell contacts

“…Our data support parts of our earlier model on the integration of mechanisms leading to a continuum of axial patterning in C. elegans (Pohl, 2015): It was previously shown that Wnt signaling, known to regulate chiral morphogenesis, is also required for chiral, counter-rotating flow during skewing of the ABa/ABp division (Naganathan et al, 2014). Based on these findings, we propose that directional cortical flow during cytokinesis of ABp might bias the distribution of Wnt pathway components such as MOM-5/Frizzled to become enriched on the ABpl/P2 interface ( Figure 5F).…”

“…Polarized activation of cortical flow and transient, avidity-driven interactions have been shown to lead to advection of anterior polarity factors (aPARs) PAR-3, PAR-6, and PKC-3, thereby establishing the anteroposterior axis in C. elegans (Munro et al, 2004;Goehring et al, 2011;Dickinson et al, 2017;Wang et al, 2017;Mittasch et al, 2018). In addition to patterning the anteroposterior axis, where longitudinal cortical flow is required, dorsoventral and left/right (l/r) patterning in C. elegans require rotational cortical flow (Singh and Pohl, 2014;Naganathan et al, 2014;Pohl, 2015;Sugioka and Bowerman, 2018). Rotational flow emerges after formation of cell-cell contacts, where contact-dependent asymmetries determine cortical flow dynamics, which in turn determine spindle orientation through coupling to microtubule dynamics (Sugioka and Bowerman, 2018).…”

Spatial integration of mechanical forces by alpha-actinin establishes actin network symmetry

“…The rules describing the physical regulation of cell size and shape are becoming better understood (Marshall, 2015;Paluch and Heisenberg, 2009;Barnhart et al, 2011;Albert and Schwarz, 2014). However, despite a wealth of information about symmetry breaking (Pohl et al, 2015), the rules describing how cell symmetry is regulated are less clear. Cell symetry is a signature of how geometrical and mechanical consistency is maintained within a cell.…”

What determines direction of asymmetry: genes, environment or chance?

“…One common theme emerges from studies of molecular mechanisms: asymmetry at the macroscopic level can often be traced back to subcellular (e.g. cytoskeletal) asymmetries, a connection expected on theoretical grounds [10,14,15]. But these studies focus almost exclusively on model taxa with fixed asymmetries (little or no variation within species) where development of asymmetry is deterministic.…”