Injury-stimulated Hedgehog signaling promotes regenerative proliferation of Drosophila intestinal stem cells

Aiguo Tian, Qing Shi, Alice Jiang, Shuangxi Li, Bing Wang, Jin Jiang

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

Many adult tissues are maintained by resident stem cells that elevate their proliferation in response to injury. The regulatory mechanisms underlying regenerative proliferation are still poorly understood. Here we show that injury induces Hedgehog (Hh) signaling in enteroblasts (EBs) to promote intestinal stem cell (ISC) proliferation in Drosophila melanogaster adult midgut. Elevated Hh signaling by patched (ptc) mutations drove ISC proliferation noncell autonomously. Inhibition of Hh signaling in the ISC lineage compromised injury-induced ISC proliferation but had little if any effect on homeostatic proliferation. Hh signaling acted in EBs to regulate the production of Upd2, which activated the JAK-STAT pathway to promote ISC 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.

Original languageEnglish (US)
Pages (from-to)807-819
Number of pages13
JournalJournal of Cell Biology
Volume208
Issue number6
DOIs
StatePublished - 2015

ASJC Scopus subject areas

  • Cell Biology

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