TY - GEN KW - Cnidarian KW - Nesseltier KW - ECM KW - Mesoglea ID - heidok34469 Y1 - 2024/// TI - Molecular Atlas and Developmental Dynamics of the Nematostella vectensis Mesoglea CY - Heidelberg AV - public N2 - Cnidarians (corals, jellyfish and sea anemones) constitute ideal model systems to investigate the dynamics and interactions of extracellular matrix (ECM) components. Many cnidarians undergo a complex life cycle characterized by transitions through different life stages with distinct morphologies. These morphological changes recapitulate developmental processes observed in vertebrates and involve the synthesis, degradation and remodeling of the ECM. The simple body plan of cnidarians provides exceptional accessibility for ECM imaging and manipulation, and previous studies have shown that the cnidarian ECM shares striking compositional and structural similarities with the vertebrate ECM. However, a major hurdle in the investigation of the cnidarian ECM is the lack of fully annotated ECM datasets allowing for a deeper understanding of its interactions and functions. In this thesis, I used the starlet sea anemone Nematostella vectensis as a model system to fully characterize the components of the cnidarian ECM by a combination of electron microscopy, single cell transcriptomics, in silico matrisome prediction and mass spectroscopic analysis of isolated ECM from three life stages (larvae, primary polyp and adult). I present the fully annotated in silico matrisome comprising 843 proteins, categorized into 246 core matrisome, 309 matrisome-associated and 289 other ECM-like proteins. 182 of these components are specific to the cnidocysts. My research revealed that the primary source of ECM is the gastroderm while the contribution of the ectoderm to ECM production is minimal. The integration of single cell transcriptome analysis and stage-specific mass spectrometry unraveled dramatic changes of the ECM during development, showing that the basal lamina gets established well in advance of the fibrillar interstitial matrix. Among the various ECM components upregulated during the larva-to-polyp transition, I detected an expanded polydom/SVEP1 family in Nematostella. This family encompasses several novel proteins, one of which emerges as a promising candidate for genetic perturbation using shRNAs. The resulting knockdown phenotype displayed defects in epithelial organization, body elongation, and development of internal mesenteries. This underscores that individual ECM components can heavily affect crucial developmental processes. In summary, my work establishes a foundational framework for future studies of the ECM by providing the first annotated molecular atlas for a cnidarian life cycle. In addition, it provides evidence for an ancient specification of ECM-producing cells within the endomesodermal lineage, along with a hierarchical function of basement membrane and interstitial matrix components in the life history of Nematostella. UR - https://archiv.ub.uni-heidelberg.de/volltextserver/34469/ A1 - Bergheim, Bruno Gideon ER -