Injury-stimulated Hedgehog signaling promotes regenerative proliferation of Drosophila intestinal stem cells.
Bottom Line: Many adult tissues are maintained by resident stem cells that elevate their proliferation in response to injury.Here we show that injury induces Hedgehog (Hh) signaling in enteroblasts (EBs) to promote intestinal stem cell (ISC) proliferation in Drosophila melanogaster adult midgut.Hence, our study uncovers a JNK-Hh-JAK-STAT signaling axis in the regulation of regenerative stem cell proliferation.
Affiliation: Department of Developmental Biology and Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390.Show MeSH
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Mentions: If DSS-mediated tissue damage stimulates ISC proliferation through the Hh signaling pathway, one would predict that feeding adult flies with DSS should induce Udp2 production and activate the JAK–STAT pathway. Indeed, we found that the JAK–STAT pathway reporter gene 10XStat-dGFP was activated in response to DSS treatment and that DSS-induced up-regulation of 10XStat-dGFP was blocked by inactivation of Hh signaling in EBs (Su(H)ts>SmoRNAi; Fig. 6, A–B′). Furthermore, knockdown of STAT in precursor cells (esgts>StatRNAi) blocked DSS-induced ISC proliferation (Fig. 6, C–G), suggesting that DSS-mediated tissue damage stimulates ISC through the JAK–STAT pathway.
Affiliation: Department of Developmental Biology and Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390.