Collagen IV and basement membrane at the evolutionary dawn of metazoan tissues

Abstract

The role of the cellular microenvironment in enabling metazoan tissue genesis remains obscure. Ctenophora has recently emerged as one of the earliest-branching extant animal phyla, providing a unique opportunity to explore the evolutionary role of the cellular microenvironment in tissue genesis. Here, we characterized the extracellular matrix (ECM), with a focus on collagen IV and its variant, spongin short-chain collagens, of non-bilaterian animal phyla. We identified basement membrane (BM) and collagen IV in Ctenophora, and show that the structural and genomic features of collagen IV are homologous to those of non-bilaterian animal phyla and Bilateria. Yet, ctenophore features are more diverse and distinct, expressing up to twenty genes compared to six in vertebrates. Moreover, collagen IV is absent in unicellular sister-groups. Collectively, we conclude that collagen IV and its variant, spongin, are primordial components of the extracellular microenvironment, and as a component of BM, collagen IV enabled the assembly of a fundamental architectural unit for multicellular tissue genesis.The emergence of the diversity of multicellular animals involved cells joining together to form tissues and organs. The ‘glue’ that enabled the cells to work together is made of rope-like molecules called collagen, which assemble into scaffolds. These smart scaffolds tether proteins forming basement membranes that connect cells, provide strength to tissues, and transmit information that influences how the cells behave.How did collagen evolve over millions of years to enable the ever-increasing complexity, size and diversity of animals? To investigate, Fidler, Darris, Chetyrkin et al. explored the tissues of the most ancient of currently living animals – the comb jellies and sponges. This revealed that among all the collagens that make up the human body, a type called collagen IV was a key innovation that enabled single celled organisms to evolve into multicellular animals. Collagen IV, as molecular glue, enabled the formation of a fundamental architectural unit of basement membrane and cells that allowed multicellular tissues and organs to evolve.The findings presented by Fidler, Darris, Chetyrkin et al. pose questions about how collagen IV glues cells together, and how information is stored in the rope-like scaffolds to influence cell behavior. Understanding these processes could ultimately lead to the development of new treatments for diseases in which the collagen smart scaffolds play a key role, such as in kidney diseases and cancer.