Going with the flow: insights fromCaenorhabditis eleganszygote polarization

Abstract

Cell polarity is the asymmetric distribution of cellular components along a defined axis. Polarity relies on complex signalling networks between conserved patterning proteins, including the PAR ( par titioning defective) proteins, which become segregated in response to upstream symmetry breaking cues. Although the mechanisms that drive the asymmetric localization of these proteins are dependent upon cell type and context, in many cases the regulation of actomyosin cytoskeleton dynamics is central to the transport, recruitment and/or stabilization of these polarity effectors into defined subcellular domains. The transport or advection of PAR proteins by an actomyosin flow was first observed in the Caenorhabditis elegan s zygote more than a decade ago. Since then a multifaceted approach, using molecular methods, high-throughput screens, and biophysical and computational models, has revealed further aspects of this flow and how polarity regulators respond to and modulate it. Here, we review recent findings on the interplay between actomyosin flow and the PAR patterning networks in the polarization of the C. elegans zygote. We also discuss how these discoveries and developed methods are shaping our understanding of other flow-dependent polarizing systems. This article is part of a discussion meeting issue ‘Contemporary morphogenesis’.

Actin-dependent membrane polarization reveals the mechanical nature of the neuroblast polarity cycle

“…A key step in Par complex function is formation of the Par domain, a continuous region along the cell membrane containing the Par complex proteins Par-6 and atypical protein kinase C (aPKC). Formation of the Par domain is a highly dynamic process involving recruitment from the cytoplasm and movement along the membrane ( Gubieda et al, 2020 ; Illukkumbura et al, 2020 ; Sunchu and Cabernard, 2020 ). In asymmetrically dividing Drosophila neuroblasts, for example, initially cytoplasmic Par-6 and aPKC accumulate in the membrane’s apical hemisphere early in mitosis ( Wodarz et al, 2000 ; Petronczki and Knoblich, 2001 ; Rolls et al, 2003 ; Homem and Knoblich, 2012 ).…”

Contemporary morphogenesis

“…Symmetry breaking is another key step in axis establishment and the development of inherently asymmetric organs. Mechanistic links between symmetry breaking and morphogenesis are explored in a number of contexts, including how actin flows drive polarity formation in the Caenorhabditis elegans zygote [20], asymmetric patterning in lineage segregation during early mouse development [21], and how mechanical asymmetries promote tissue folding [22]. Finally, we review how changes in cell states from epithelial to mesenchymal (and vice versa) are controlled and coordinated to facilitate tissue morphogenesis [23].…”

PLK-1 Regulation of Asymmetric Cell Division in the Early C. elegans Embryo

“…These cues trigger the establishment of polarity, which takes roughly 10 min and results in the concentration of the aPARs at the anterior cortex and the pPARs at the posterior cortex. During polarity establishment, anteriorly-directed cortical actomyosin flows help to sweep the cortical aPARs out of the posterior domain, thereby allowing pPARs to load from the cytoplasm onto the posterior cortex (Cheeks et al, 2004 ; Munro et al, 2004 ; Goehring et al, 2011 ; Gubieda et al, 2020 ). These asymmetries are maintained for ~10 min until the embryo divides.…”