Trachea-Derived Dpp Controls Adult Midgut Homeostasis in Drosophila

Li, Zhouhua; Zhang, Yan; Han, Li‐Li; Shi, Lai; Lin, Xinhua

doi:10.1016/j.devcel.2012.12.010

Cited by 117 publications

(157 citation statements)

References 44 publications

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“…During embryonic gut formation Dpp is required in a complex feedback, both within and between tissue layers, to maintain the correct patterning of homeotic gene expression during midgut morphogenesis [46,47]. In the Drosophila adult gut, Dpp has multiple complex roles in the regulation of ISCs in both an autocrine and paracrine mode [48][49][50][51][52][53]. Additionally, the TGF-β/ activin pathway acts as a carbohydrate-sensing mechanism in the adult midgut to regulate digestive enzyme expression [54].…”

Section: Discussionmentioning

confidence: 99%

Dpp regulates autophagy-dependent midgut removal and signals to block ecdysone production

Denton

Dayan

et al. 2018

Cell Death Differ

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Animal development and homeostasis require the programmed removal of cells. Autophagy-dependent cell deletion is a unique form of cell death often involved in bulk degradation of tissues. In Drosophila the steroid hormone ecdysone controls developmental transitions and triggers the autophagy-dependent removal of the obsolete larval midgut. The production of ecdysone is exquisitely coordinated with signals from numerous organ systems to mediate the correct timing of such developmental programs. Here we report an unexpected role for the Drosophila bone morphogenetic protein/transforming growth factor β ligand, Decapentaplegic (Dpp), in the regulation of ecdysone-mediated midgut degradation. We show that blocking Dpp signaling induces premature autophagy, rapid cell death, and midgut degradation, whereas sustained Dpp signaling inhibits autophagy induction. Furthermore, Dpp signaling in the midgut prevents the expression of ecdysone responsive genes and impairs ecdysone production in the prothoracic gland. We propose that Dpp has dual roles: one within the midgut to prevent improper tissue degradation, and one in interorgan communication to coordinate ecdysone biosynthesis and developmental timing.

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Section: Discussionmentioning

confidence: 99%

Dpp regulates autophagy-dependent midgut removal and signals to block ecdysone production

Denton

Dayan

et al. 2018

Cell Death Differ

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“…Many conserved signal transduction pathways regulate ISC behavior following injury, including the EGF, JAK/STAT, Wingless/Wnt, TGF-β/Dpp and insulin pathways (Biteau and Jasper, 2011;Choi et al, 2011;Cordero et al, 2012;Guo et al, 2013;Jiang et al, , 2009Lee et al, 2009;Li et al, 2013b;O'Brien et al, 2011;Tian and Jiang, 2014;Xu et al, 2011). The interplay between these different signaling pathways ensures homeostatic renewal as well as rapid regenerative responses to injury.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2016

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

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“…This allows the rapid regeneration of the compromised gut and maintains barrier integrity (4,22,90). The activity of a number of pathways, namely the JAK-STAT, epidermal growth factor (EGF) receptor, decapentaplegic (DPP), and Wingless/Myc pathways, stimulates the proliferation and differentiation of progenitor cells into enterocytes (40,72,90,105; see References 89, 176 for reviews). Upon damage, these pathways are activated by the release of EGFs, Wingless, and JAK-STAT ligands (Upd3, Upd2) from damaged enterocytes or progenitors, thus establishing a compensatory homeostatic loop.…”

Section: The Drosophila Gut: a Plastic Organmentioning

confidence: 99%

The Digestive Tract of Drosophila melanogaster

2013

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The digestive tract plays a central role in the digestion and absorption of nutrients. Far from being a passive tube, it provides the first line of defense against pathogens and maintains energy homeostasis by exchanging neuronal and endocrine signals with other organs. Historically neglected, the gut of the fruit fly Drosophila melanogaster has recently come to the forefront of Drosophila research. Areas as diverse as stem cell biology, neurobiology, metabolism, and immunity are benefitting from the ability to study the genetics of development, growth regulation, and physiology in the same organ. In this review, we summarize our knowledge of the Drosophila digestive tract, with an emphasis on the adult midgut and its functional underpinnings. 377

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Trachea-Derived Dpp Controls Adult Midgut Homeostasis in Drosophila

Cited by 117 publications

References 44 publications

Dpp regulates autophagy-dependent midgut removal and signals to block ecdysone production

Dpp regulates autophagy-dependent midgut removal and signals to block ecdysone production

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

The Digestive Tract of Drosophila melanogaster

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