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: The observation that Hh signaling is not essential for basal ISC proliferation but is required for damage-induced ISC proliferation prompted us to examine whether Hh pathway activity is up-regulated in response to injury. Using RT-qPCR, we found that the expression of the Hh pathway target gene ptc as well as hh itself was up-regulated in guts treated with DSS; however, expression of hh was not induced by bleomycin treatment (Fig. 5 A and Fig. S2).
Affiliation: Department of Developmental Biology and Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390.