Abstract
How living systems break symmetry in an organized manner is a fundamental question in biology. In wild-type Caenorhabditis elegans zygotes, symmetry breaking during anterior-posterior axis specification is guided by centrosomes, resulting in anterior-directed cortical flows and a single posterior PAR-2 domain. We uncover that C. elegans zygotes depleted of the Aurora A kinase AIR-1 or lacking centrosomes entirely usually establish two posterior PAR-2 domains, one at each pole. We demonstrate that AIR-1 prevents symmetry breaking early in the cell cycle, whereas centrosomal AIR-1 instructs polarity initiation thereafter. Using triangular microfabricated chambers, we establish that bipolarity of air-1(RNAi) embryos occurs effectively in a cell-shape and curvature-dependent manner. Furthermore, we develop an integrated physical description of symmetry breaking, wherein local PAR-2-dependent weakening of the actin cortex, together with mutual inhibition of anterior and posterior PAR proteins, provides a mechanism for spontaneous symmetry breaking without centrosomes.
Highlights
Symmetry breaking is a fundamental feature of living systems, operating at different scales and in different contexts
While examining the function of AIR-1 in spindle positioning (Kotak et al, 2016), as noted previously (Noatynska et al, 2010; Schumacher et al, 1998), we observed that the majority of zygotes in which AIR-1 had been depleted by RNAi exhibited a remarkable polarity phenotype, with two distinct PAR-2 domains, one at each pole
Since polarity establishment normally relies in a partially redundant manner on local RHO-1 inactivation mediated by cortical flows and on the PAR-2-dependent pathway (Motegi et al, 2011), we investigated these mechanisms in air-1(RNAi) embryos to assess whether their alteration could be responsible for imparting bipolarity
Summary
Symmetry breaking is a fundamental feature of living systems, operating at different scales and in different contexts. One critical instance occurs at the onset of development, when symmetry must be broken in a tightly coordinated manner to ensure correct specification of body axes. The zygote of the nematode Caenorhabditis elegans is a powerful model system for dissecting the mechanisms that govern symmetry breaking and anterior-posterior (A-P) axis specification (reviewed in Rose and Gonczy, 2014). The zygote undergoes the two female meiotic divisions, leading to extrusion of the polar bodies, usually at the future anterior pole. Thereafter, the RHO-1 guanine-nucleotide-exchange factor (GEF) ECT-2 is cleared from the cortex in the vicinity of the sperm-contributed centrioles, which are usually located on the opposite side from the polar bodies, leading to local RHO-1 inactivation and Klinkert et al eLife 2019;8:e44552.
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