Hydra Mesoglea Proteome Identifies Thrombospondin as a Conserved Component Active in Head Organizer Restriction

• Published in: Scientific reports Vol. 8; no. 1; pp. 11753 - 18
• Main Authors: Lommel, Mark, Strompen, Jennifer, Hellewell, Andrew L., Balasubramanian, Gnana Prakash, Christofidou, Elena D., Thomson, Andrew R., Boyle, Aimee L., Woolfson, Derek N., Puglisi, Kane, Hartl, Markus, Holstein, Thomas W., Adams, Josephine C., Özbek, Suat
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 06.08.2018; Nature Publishing Group
• Subjects: 13/1; 38/32; 42/89; 45/15; 631/136/1660/1993; 631/181/2806; 631/80/86/2370; 82; 82/58; 96/95; Animals; beta Catenin - genetics; beta Catenin - metabolism; Biochemistry; Body Patterning - genetics; Body Patterning - physiology; Chromatin; Connective tissue; Genomes; Glycoproteins; Homeostasis; Humanities and Social Sciences; Hydra - metabolism; Immunoprecipitation; Mammals; Mass spectrometry; multidisciplinary; Next-generation sequencing; Peptides; Phylogenetics; Phylogeny; Polyps (organisms); Promoter Regions, Genetic - genetics; Proteins; Proteome - genetics; Proteome - metabolism; Proteomes; RNA, Small Interfering - genetics; Science; Science (multidisciplinary); Scientific imaging; Signal Transduction - genetics; Signal Transduction - physiology; siRNA; Thrombospondin; Thrombospondins - genetics; Thrombospondins - metabolism; Wnt protein; Wnt Proteins - genetics; Wnt Proteins - metabolism; β-Catenin
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-30035-2

Thrombospondins (TSPs) are multidomain glycoproteins with complex matricellular functions in tissue homeostasis and remodeling. We describe a novel role of TSP as a Wnt signaling target in the basal eumetazoan Hydra . Proteome analysis identified Hydra magnipapillata TSP (HmTSP) as a major component of the cnidarian mesoglea. In general, the domain organization of cnidarian TSPs is related to the pentameric TSPs of bilaterians, and in phylogenetic analyses cnidarian TSPs formed a separate clade of high sequence diversity. HmTSP expression in polyps was restricted to the hypostomal tip and tentacle bases that harbor Wnt-regulated organizer tissues. In the hypostome, HmTSP- and Wnt3 -expressing cells were identical or in close vicinity to each other, and regions of ectopic tentacle formation induced by pharmacological β-Catenin activation (Alsterpaullone) corresponded to foci of HmTSP expression. Chromatin immunoprecipitation (ChIP) confirmed binding of Hydra TCF to conserved elements in the HmTSP promotor region. Accordingly, β-Catenin knockdown by siRNAs reduced normal HmTSP expression at the head organizer. In contrast, knockdown of HmTSP expression led to increased numbers of ectopic organizers in Alsterpaullone-treated animals, indicating a negative regulatory function. Our data suggest an unexpected role for HmTSP as a feedback inhibitor of Wnt signaling during Hydra body axis patterning and maintenance.