Injury-induced BMP signaling negatively regulates <i>Drosophila</i> midgut homeostasis

Guo, Zheng; Driver, Ian; Ohlstein, Benjamin

doi:10.1083/jcb.201302049

Cited by 139 publications

(214 citation statements)

References 67 publications

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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%

“…Previous studies had revealed that several signal transduction pathways are important to control ISC proliferation, in particular the JAK/STAT, epidermal growth factor (EGF) and Decapentaplegic (Dpp)/TGF-β pathways (Biteau and Jasper, 2011;Guo et et al, 2011). We therefore examined whether knockdown of Tnks in ECs resulted in increased expression of the ligands from these pathways using RT-qPCR.…”

Section: Non-autonomous Control Of Jak/stat Signaling In Iscs By Wingmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Non-autonomous Control Of Jak/stat Signaling In Iscs By Wingmentioning

confidence: 99%

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

et al. 2016

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“…Recent studies have revealed an important role for Decapentaplegic (Dpp) signaling in the differentiation of CCs in adult Drosophila [22,23]. GSSCs that are mutant for Dpp signaling components, such as the receptor Thickvein (Tkv) or the downstream transcriptional factor Mothers against Dpp (Mad), can no longer effectively produce CCs [22,23].…”

Section: Notch Activation Is Sufficient To Induce Cc/is Cell Differenmentioning

confidence: 99%

“…GSSCs that are mutant for Dpp signaling components, such as the receptor Thickvein (Tkv) or the downstream transcriptional factor Mothers against Dpp (Mad), can no longer effectively produce CCs [22,23]. To understand the epistatic relationships between Notch and Dpp signaling in CC differentiation, we asked whether forced expression of N icd could induce differentiation of tkv or mad mutant progenitor cells.…”

Section: Notch Activation Is Sufficient To Induce Cc/is Cell Differenmentioning

confidence: 99%

EGFR and Notch signaling respectively regulate proliferative activity and multiple cell lineage differentiation of Drosophila gastric stem cells

Wang

Guo

2014

Cell Res

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Quiescent, multipotent gastric stem cells (GSSCs) in the copper cell region of adult Drosophila midgut can produce all epithelial cell lineages found in the region, including acid-secreting copper cells, interstitial cells and enteroendocrine cells, but mechanisms controlling their quiescence and the ternary lineage differentiation are unknown. By using cell ablation or damage-induced regeneration assays combined with cell lineage tracing and genetic analysis, here we demonstrate that Delta (Dl)-expressing cells in the copper cell region are the authentic GSSCs that can self-renew and continuously regenerate the gastric epithelium after a sustained damage. Lineage tracing analysis reveals that the committed GSSC daughter with activated Notch will invariably differentiate into either a copper cell or an interstitial cell, but not the enteroendocrine cell lineage, and loss-of-function and gainof-function studies revealed that Notch signaling is both necessary and sufficient for copper cell/interstitial cell differentiation. We also demonstrate that elevated epidermal growth factor receptor (EGFR) signaling, which is achieved by the activation of ligand Vein from the surrounding muscle cells and ligand Spitz from progenitor cells, mediates the regenerative proliferation of GSSCs following damage. Taken together, we demonstrate that Dl is a specific marker for Drosophila GSSCs, whose cell cycle status is dependent on the levels of EGFR signaling activity, and the Notch signaling has a central role in controlling cell lineage differentiation from GSSCs by separating copper/interstitial cell lineage from enteroendocrine cell lineage.

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“…Finally, activation of DPP/BMP signalling is required for the return to homeostasis after repair of the damage epithelium has been achieved (Zhou et al, 2014) (Guo et al, 2013).…”

Section: Intestinal Stem Cell Homeostasis During Tissue Regenerationmentioning

confidence: 99%

Intestinal stem cell proliferation and epithelial homeostasis in the adult Drosophila midgut

Nászai

Carroll

Cordero

2015

Insect Biochemistry and Molecular Biology

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Adult tissue homeostasis requires a tight balance between the removal of old or damaged cells and the production of new ones. Such processes are usually driven by dedicated stem cells that reside within specific tissue locations or niches (Nystul and Spradling, 2006).The intestinal epithelium has a remarkable regenerative capacity, which has made it a prime paradigm for the study of stem cell-driven tissue self-renewal. The discovery of the presence of stem cells in the adult midgut of the fruit fly Drosophila melanogaster has significantly impacted our understanding of the role of stem cells in intestinal homeostasis. Here we will review the current knowledge of the main mechanisms involved in the regulation of tissue homeostasis in the adult Drosophila midgut, with a focus on the role of stem cells in this process. We will also discuss processes involving acute or chronic disruption of normal intestinal homeostasis such as damage-induced regeneration and ageing.3

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Injury-induced BMP signaling negatively regulates Drosophila midgut homeostasis

Abstract: Injury-induced BMP signaling in the midgut negatively regulates intestinal stem cell division, whereas regional constitutive BMP signaling promotes copper cell differentiation.

Cited by 139 publications

References 67 publications

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

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

EGFR and Notch signaling respectively regulate proliferative activity and multiple cell lineage differentiation of Drosophila gastric stem cells

Intestinal stem cell proliferation and epithelial homeostasis in the adult Drosophila midgut

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