The ADP-ribose polymerase Tankyrase regulates adult intestinal stem cell proliferation during homeostasis inDrosophila

摘要: Wnt/β-catenin signaling controls intestinal stem cell (ISC) proliferation, and is aberrantly activated in colorectal cancer. Inhibitors of the ADP-ribose polymerase Tankyrase (Tnks) have become lead therapeutic candidates for Wnt-driven cancers, following recent discovery that Tnks targets Axin, a negative regulator Wnt signaling, proteolysis. Initial reports indicated important pathway activation cultured human lines. However, requirement physiological settings has been less clear, as subsequent studies mice, fish flies suggested was either entirely dispensable Wnt-dependent processes vivo, or alternatively, had tissue-specific roles. Here, using null alleles, we demonstrate regulation Axin by highly conserved Drosophila homolog essential control ISC proliferation. Furthermore, adult intestine, where activity Wingless graded peaks at each compartmental boundary, regions high, but relatively low. Finally, observed previously components, absorptive enterocytes proliferation neighboring ISCs non-autonomously regulating JAK/STAT signaling. These findings reveal suggest an role amplification with relevance development, homeostasis