Systemic coordination of whole-body tissue remodeling during local regeneration in sea anemones

The complexity of regeneration extends beyond local wound responses, eliciting systemic processes engaging the entire organism. However, their functional relevance, and the spatial and temporal orchestration of the underlying molecular processes distant from the injury site remain unknown. Here, we demonstrate that local regeneration in the cnidarian Nematostella vectensis involves a systemic homeostatic response, leading to coordinated whole-body remodeling. Leveraging spatial transcriptomics, endogenous protein tagging, and live imaging, we comprehensively dissect this systemic response at the organismal scale. We identify proteolysis as critical process driven by both local and systemic upregulation of metalloproteases. We show that metalloproteinase expression levels and activity scale with the extent of tissue loss, leading to proportional long-range movement of tissue and its associated extracellular matrix. Our findings demonstrate the adaptive nature of the systematic response in regeneration. We propose that this integrated regenerative mechanism enables the organism to maintain shape homeostasis while coping with injuries.