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: Many types of cellular stresses can activate the JNK pathway (Weston and Davis, 2007). Indeed, we found that midguts fed with DSS activated the JNK pathway reporter puc-lacZ in Su(H)>GFP+ EBs as well as adjacent ECs, whereas mock treatment barely activated puc-lacZ in these cells (Fig. 7, A–B′). To determine whether JNK pathway activation is required for DSS-induced Hh pathway activation, we blocked the JNK pathway by expressing a dominant-negative Basket, BskDN, in EBs (Su(H)ts>BskDN). We found that Su(H)ts>BskDN blocked DSS-induced Hh up-regulation and ISC proliferation (Fig. 7, C and D).
Affiliation: Department of Developmental Biology and Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390.