biostudies-literatureMackay DJNovo Nordisk Fonden (Novo Nordisk Foundation)Carlsbergfondet (Carlsberg Foundation)8597https://www.ebi.ac.uk/biostudies/studies/S-EPMC12480979biostudies-literatureUnknown16(1)In adult tissues, stem cells (SCs) reside in specialized niches, where they remain relatively stationary state until activated by injury. While migration is essential for regeneration, mechanisms guiding SCs towards injury sites remain poorly understood due to challenges in tracking them in vivo. Here, we present an experimental framework to monitor intestinal SC (ISC) movement in real time during early gut regeneration. We identify the Drosophila PDGF-VEGF-related receptor, Pvr, as a critical regulator of this process, with ISC-specific Pvr depletion strongly impairing migration and regeneration. The ligand, Pvf1, produced by gut-associated trachea after damage, serves as a guidance cue directing ISCs towards injury sites. Our work highlights a critical role of gut-trachea crosstalk in guNature communicationsPvf1-Pvr-mediated crosstalk between trachea and gut guides intestinal stem cell migration to promote gut regeneration.PMC12480979NNF180C0033920CF19-0353CF23-1302Andersen DSColombani JMackay DJConnolly ETanari ABRauzi MJohn AChristensen CFLoudhaief RfalsePvf1-Pvr-mediated crosstalk between trachea and gut guides intestinal stem cell migration to promote gut regeneration.In adult tissues, stem cells (SCs) reside in specialized niches, where they remain relatively stationary state until activated by injury. While migration is essential for regeneration, mechanisms guiding SCs towards injury sites remain poorly understood due to challenges in tracking them in vivo. Here, we present an experimental framework to monitor intestinal SC (ISC) movement in real time during early gut regeneration. We identify the Drosophila PDGF-VEGF-related receptor, Pvr, as a critical regulator of this process, with ISC-specific Pvr depletion strongly impairing migration and regeneration. The ligand, Pvf1, produced by gut-associated trachea after damage, serves as a guidance cue directing ISCs towards injury sites. Our work highlights a critical role of gut-trachea crosstalk in gu2025-01-01T00:00:00Z2025 Sep2026-06-03T23:28:36.179Z2026-05-03T03:11:46.129ZS-EPMC124809794102277810.1038/s41467-025-63704-8