Non-Canonical Wnt Signaling Promotes Directed Migration of Intestinal Stem Cells to Sites of Injury

The study demonstrates that enteroendocrine cells (EEs) play a crucial role in tissue regeneration after injury by coordinating stem cell migration towards the wound in the Drosophila intestinal epithelium. When an injury occurs, EEs release the N-terminal domain of the PTK7 orthologue, Otk, which activates non-canonical Wnt signaling in intestinal stem cells (ISCs). This activation promotes the formation of actin-based protrusions and encourages ISCs to migrate towards the wound. This migratory behavior is closely linked to ISC proliferation and is necessary for efficient tissue repair during injury. The findings underscore the importance of non-canonical Wnt signaling in the regeneration of the intestinal epithelium and identify EE-released ligands as critical coordinators of ISC migration.