Poster Presentation Hunter Cell Biology Meeting 2025

An ancient interplay between Scribble, Dlg and Vangl controls regeneration in the simplest animal on earth, Trichoplax (#202)

Patrick O Humbert 1
  1. La Trobe Institute For Molecular Science, La Trobe University, Bundoora, VIC, Australia

How is the architecture of an animal tissue established and maintained? One of the key evolutionary events of life on earth is the emergence of organisms that use multiple cell types for the division of labour, the first animal. How this occurred and how multicellular organisms (metazoans) establish and maintain an organized architecture is still poorly understood. Here, we utilise Trichoplax adhaerens, one of the simplest and most ancient multicellular animals to identify universal mechanisms of tissue organisation and repair. Because of its size, ability to regenerate and its simplicity, Trichoplax provides a great model to identify the original cell polarity mechanisms required in the first multicellular animals.

 In this study, we used complementary structural and functional approaches to examine Trichoplax Scrib (TaScrib), Dlg (TaDlg), and Vangl-like (TaVangl) proteins in the Placozoan species Trichoplax Sp. H2. We show that the key domains required for Scrib and Dlg mediated polarity signalling, their PDZ domains, not only harbour a highly conserved structure, but also display comparable affinities for the planar cell polarity regulator TaVangl, with key atomic interactions between Vangl and Scrib conserved between human and Trichoplax protein complexes. We show that in Trichoplax, TaScrib and TaDlg co-localise apicobasally in epithelial cells, and that together with TaVangl, TaScrib and TaDlg are functionally required for the proper wound healing and tissue regeneration of Trichoplax.

Collectively, we demonstrate the ancient and conserved nature of cell polarity mechanisms in regeneration from individual hydrogen bonds to whole-animal behaviour extending evolutionarily from humans to one of the first multicellular organisms, Trichoplax. I will also describe how we are utilising Trichoplax as a new animal model to probe how gravity, one of the only constant forces present throughout evolution, may have informed the earliest mechanisms for the establishment and maintenance of tissue architecture of the first epithelia.