The PAR proteins are best known for their conserved roles in establishing cell polarity during development. Four studies now shed light on their cytoskeletal interactions in contrasting developmental contexts.
Apical constriction, powered by actomyosin (AM) contractility, drives cell internalisation during morphogenesis. To investigate PAR complex (Par-6, aPKC and Bazooka/Par-3) protein functions in apical constriction, Tony Harris and colleagues studied dorsal closure (DC) in Drosophila, in which amnioserosal cells undergo pulsed contractions (see p. 1645). By performing live imaging on GFP-tagged embryos, they observed amnioserosal cells undergoing repeated cycles of (apically restricted) AM network assembly and disassembly during DC. As these networks form, they interact transiently with an apically localised Par-6/aPKC/Par-3 PAR complex, report the authors, with each assembly event driving apical constriction. Strikingly, their live imaging results combined with genetic interaction tests reveal that different PAR proteins regulate distinct phases of the assembly/disassembly cycle, with Par-3 promoting the network's duration and Par-6/aPKC promoting the lull time between pulses. Together, these findings reveal how the PAR complex regulates the mechanics of AM contractility during apical constriction.
The C. elegans zygote is also a classic model for studying cell polarity, in which cortical flows created by AM network contractions mobilise the anterior PAR proteins (PAR-3, PAR-6 and PKC-3) away from the future posterior end of the embryo, as marked by the sperm centrosome and the posterior PAR-1 and PAR-2. The Rho-GEF ECT-2 is central to establishing these early cortical flows. Now Geraldine Seydoux's lab report that a second, parallel and redundant, PAR-2-dependent pathway can polarise the zygote in the absence of ECT-2-dependent cortical flows (see p. 1669). They show that PAR-2 localises to the cortex nearest the sperm centrosome, even when cortical flows are absent, where it antagonises the PAR-3-dependent recruitment of myosin. This creates myosin flows that transport the anterior PAR complex away from PAR-2 in a positive-feedback loop. The authors propose that this second polarity pathway strengthens the robustness of the initial polarity cue provided by the sperm centrosome. In a separate study of early embryo polarisation on p. 1765, Daniel St Johnston and colleagues report that in a new Drosophila Par-3 mutant, oocyte polarity is, surprisingly, normal but axis formation is not. Importantly, they show that when Par-3 is absent, the main anteroposterior and dorsoventral axis determinants are mislocalised. From their findings, the authors propose that a Par-1-activating kinase cascade, rather than cortical contractions, generate the initial AP asymmetry in fly embryos.
Finally, Carrie Cowan and colleagues, on p. 1743, highlight in C. elegans embryos the role of PAR proteins in asymmetric cell divisions, in which the boundary between the anterior and posterior PAR domains is matched to the site of cell division to ensure the correct segregation of cell fate determinants to daughter cells. They report that cell polarity and cell division are coordinated by a novel mechanism involving the repositioning of the PAR-2 boundary via a Gα pathway that repositions the boundary between the PAR domains to match the cytokinesis furrow. It does so by regulating microtubule-cortex interactions to cause large-scale cortical reorganisation that moves PAR-2 towards the furrow. This mechanism, the authors suggest, could also exist in asymmetric divisions of more complex systems.
- © 2010.