Injury-stimulated Hedgehog signaling promotes regenerative proliferation of Drosophila intestinal stem cells.
Bottom Line: Inhibition of Hh signaling in the ISC lineage compromised injury-induced ISC proliferation but had little if any effect on homeostatic proliferation.Furthermore, we show that Hh signaling is stimulated by DSS through the JNK pathway and that inhibition of Hh signaling in EBs prevented DSS-stimulated ISC proliferation.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.