Abstract
AbstractTissue regeneration after injury requires coordinated regulation of stem cell activation, division, and daughter cell differentiation, processes that are increasingly well understood in many regenerating tissues. How accurate stem cell positioning and localized integration of new cells into the damaged epithelium are achieved, however, remains unclear. Here, we show that enteroendocrine cells coordinate stem cell migration towards a wound in the Drosophila intestinal epithelium. In response to injury, enteroendocrine cells release the N-terminal domain of the PTK7 orthologue, Otk, which activates non-canonical Wnt signaling in intestinal stem cells, promoting actin-based protrusion formation and stem cell migration towards a wound. We find that this migratory behavior is closely linked to proliferation, and that it is required for efficient tissue repair during injury. Our findings highlight the role of non-canonical Wnt signaling in regeneration of the intestinal epithelium, and identify enteroendocrine cell-released ligands as critical coordinators of intestinal stem cell migration.
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry
Reference85 articles.
1. Dekoninck, S. & Blanpain, C. Stem cell dynamics, migration and plasticity during wound healing. Nat. Cell Biol. 21, 18–24 (2019).
2. de Lucas, B., Pérez, L. M. & Gálvez, B. G. Importance and regulation of adult stem cell migration. J. Cell Mol. Med. 22, 746–754 (2018).
3. Fu, X. et al. Mesenchymal stem cell migration and tissue repair. Cells 8, 784 (2019).
4. Wu, X. et al. Skin stem cells orchestrate directional migration by regulating microtubule-ACF7 connections through GSK3β. Cell 144, 341–352 (2011).
5. Park, S. et al. Tissue-scale coordination of cellular behaviour promotes epidermal wound repair in live mice. Nat. Cell Biol. 19, 155–163 (2017).