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Publication - Dr Deborah Shoemark

    Emergence of a Thrombospondin Superfamily at the Origin of Metazoans


    Shoemark, D, Ziegler, B, Watanabe, H, Strompen, J, Tucker, RP, Ozbek, S & Adams, J, 2019, ‘Emergence of a Thrombospondin Superfamily at the Origin of Metazoans’. Molecular Biology and Evolution, vol 36., pp. 1220-1238


    Extracellular matrix (ECM) is considered central to the evolution of metazoan
    multicellularity, however the repertoire of ECM proteins in non-bilaterians remains
    unclear. Thrombospondins (TSPs) are known to be well-conserved from cnidarians
    to vertebrates, yet to date have been considered a unique family, principally studied
    for matricellular functions in vertebrates. Through searches utilizing the highlyconserved
    C-terminal region of TSPs we identify undisclosed new families of
    thrombospondin-related proteins in metazoans, designated mega-thrombospondin,
    sushi-thrombospondin and poriferan-thrombospondin, each with a distinctive
    phylogenetic distribution. These proteins share the TSP C-terminal region domain
    architecture, as determined by domain composition and analysis of molecular
    models against known structures. Mega-thrombospondins, the only form identified in ctenophores, are typically >2700aa and are also characterized by N-terminal
    leucine-rich repeats and central cadherin/immunoglobulin domains. In cnidarians, which have a well-defined ECM, Mega-TSP was expressed throughout
    embryogenesis in Nematostella vectensis, with dynamic endodermal expression in larvae and primary polyps and widespread ectodermal expression in adult N.
    vectensis and Hydra magnipapillata polyps. Hydra Mega-TSP was also expressed
    during regeneration and siRNA-silencing of Mega-TSP in Hydra caused specific
    blockade of head regeneration. Molecular phylogenetic analyses based on the
    conserved TSP C-terminal region identified each of the TSP-related groups to form clades distinct from the canonical TSPs. We discuss models for the evolution of the newly-defined TSP superfamily by gene duplications, radiation and gene losses from a debut in the last metazoan common ancestor. Together, the data provide new insight into the evolution of ECM and tissue organization in metazoans.

    Full details in the University publications repository