Gene expression profiles of larval zebrafish under homeostatic conditions, after induced epithelial cell loss, and during tissue repair.

Formation and maintenance of an epithelial barrier is essential for defense against fungal invasion and other noxious stimuli and is fundamental to the survival of all animals. As part of homeostatic repair mechanisms, mucosal tissues eliminate damaged epithelial cells while trying to preserve barrier function. Compromised epithelial integrity following trauma is a common mode of infection, and therefore, enhancing mucosal repair may help to mitigate opportunistic invasion. However, the technical challenges to efficiently manipulate and monitor mucosal injury in vivo has thus far prevented a detailed characterization and therapeutic exploitation of key epithelial repair mechanisms. Here we establish a high-throughput mucosal injury and repair model by inducible loss of epithelial cells in larval zebrafish. Transcriptional profiling identified a significant upregulation of the epidermal growth factor receptor ligand epigen (EPGN) upon tissue damage, and we found treatment with recombinant human EPGN suppressed epithelial cell loss to maintain barrier integrity in the face of damage. This study provides key insights into the mechanisms regulating epithelial cell loss during mucosal injury and identifies key pathways associated with rapid restoration of barrier function and epithelial tissue integrity.