The basement membrane determines the choice of wound healing mechanism across wound scales in the basal eukaryote Clytia hemiphaerica

Epithelial wound healing is an essential process in multicellular organisms, primarily driven by lamellipodia-based crawling, purse-string contraction, and collective cell migration. One or more of these mechanisms participate in healing a wound, yet the choice, sequence, and coordination of these processes are poorly understood. Moreover, different mechanisms dominate in different tissues, organisms, wound types and wound sizes, further complicating our understanding of how cells select among healing mechanisms. In this study we analyzed wound healing across wound types and spatial scales in the basal eukaryote Clytia hemisphaerica (Clytia) to establish a unified model for mechanism selection within a single organism. We demonstrate that lamellipodial crawling and actomyosin cable contractions are sequential, partially redundant processes involved in healing all wounds. Furthermore, the exposure of the basement membrane acts as a central regulatory cue, orchestrating lamellipodia formation, actomyosin contraction and collective cell migration responses. Remarkably, we discovered that these same mechanisms operate in healing micro-wounds internal to a single cell. This work fundamentally advances our understanding of how diverse healing mechanisms are coordinated to respond to all types of wounds, while the use of a basal metazoan model expands our knowledge of fundamental strategies for maintaining epithelial integrity.