Ancestral roles of atypical cadherins in planar cell polarity

Abstract

Fat, Fat-like, and Dachsous family cadherins are giant proteins that regulate planar cell polarity (PCP) and cell adhesion in bilaterians. Their evolutionary origin can be traced back to prebilaterian species, but their ancestral function(s) are unknown. We identified Fat-like and Dachsous cadherins inHydra, a member of phylum Cnidaria a sister group of bilaterian. We foundHydradoes not possess a true Fat homolog, but has homologs of Fat-like (HyFatl) and Dachsous (HyDs) that localize at the apical membrane of ectodermal epithelial cells and are planar polarized perpendicular to the oral–aboral axis of the animal. Using a knockdown approach we found that HyFatl is involved in local cell alignment and cell–cell adhesion, and that reduction of HyFatl leads to defects in tissue organization in the body column. Overexpression and knockdown experiments indicate that the intracellular domain (ICD) of HyFatl affects actin organization through proline-rich repeats. Thus, planar polarization of Fat-like and Dachsous cadherins has ancient, prebilaterian origins, and Fat-like cadherins have ancient roles in cell adhesion, spindle orientation, and tissue organization.

Fat3 acts through independent cytoskeletal effectors to coordinate asymmetric cell behaviors during polarized circuit assembly

“…Versatility depends in part on the intracellular domain (ICD), which interacts with a variety of cytoplasmic effectors via discrete domains ( Sadeqzadeh et al, 2014 ). Effects on tissue polarity require interactions with cytoskeletal regulators that create local changes in cell shape, a property that is observed even in evolutionarily ancient Fat cadherins ( Brooun et al, 2020 ). Additional functional versatility is achieved by their huge extracellular domain (ECD), which receives signals and also acts non-autonomously to influence the behavior of surrounding cells ( Barlan et al, 2017 ).…”

How do the Fat–Dachsous and core planar polarity pathways act together and independently to coordinate polarized cell behaviours?

“…Cell orientation in lymphatic valve morphogenesis is also defective in Ft4 and Dchs1 mutants [175,176], although here the core pathway also regulates cell rearrangements [177,178]. Furthermore, cell shape and alignment of epithelial cells in the body column of the cnidarian Hydra is regulated by HyFat and HyDs [179]. Finally, in zebrafish Dchs1b regulates microtubule turnover via AuroraB [180,181].…”

PCP components control anterior and posterior regeneration, with a Prickle homolog impacting muscle organization, in the acoelHofstenia miamia

“…1A). Homologs of the Ft/Ds pathway components have polarized cellular localization in Hydra (Brooun et al, 2020) and homologs of the core PCP are needed for polarization of cilia in epidermal cells in planarians (Almuedo-Castillo et al, 2011; Vu et al, 2019). In the context of WBR, PCP components are involved in neural regeneration, where they limit neuronal growth (Beane et al, 2012).…”