Open AccessAxin proteolysis by Iduna is required for the regulation of stem cell proliferation and intestinal homeostasis in Drosophila
Author(s) -
Yetiş Gültekin,
Hermann Steller
Publication year - 2019
Publication title -
development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.15
H-Index - 36
eISSN - 1477-9129
pISSN - 0950-1991
DOI - 10.1242/dev.169284
Subject(s) - biology , wnt signaling pathway , microbiology and biotechnology , stem cell , ubiquitin ligase , mutant , ubiquitin , signal transduction , genetics , gene
The self-renewal of intestinal stem cell is controlled by Wingless/Wnt-β catenin signaling both in Drosophila and mammals. Since Axin is a rate-limiting factor in Wingless signaling its regulation is essential. Iduna is an evolutionarily conserved ubiquitin E3 ligase that has been identified as a critical regulator for degradation of ADP-ribosylated Axin and thus of Wnt/β-catenin signaling. However, its physiological significance remains to be demonstrated. Here, we generated loss-of-function mutants of Iduna to investigate its physiological role in Drosophila. Genetic depletion of Iduna causes the accumulation of both Tankyrase and Axin. Increase of Axin protein in enterocytes non-autonomously enhanced stem cell divisions in the Drosophila midgut. Enterocytes secreted Unpaired and thereby stimulated the activity of the JAK-STAT pathway in intestinal stem cells. A decrease in Axin gene expression suppressed both the over-proliferation of stem cells and restored their numbers to normal levels in Iduna mutants. These findings suggest that Iduna-mediated regulation of Axin proteolysis is essential to maintain tissue homeostasis in the Drosophila midgut.