Transforming Growth Factor β/Activin Signaling Functions as a Sugar-Sensing Feedback Loop to Regulate Digestive Enzyme Expression

Chng, Wen Bin Alfred; Sleiman, Maroun Bou; Schüpfer, Fanny; Lemaître, Bruno

doi:10.1016/j.celrep.2014.08.064

Cited by 90 publications

(100 citation statements)

References 50 publications

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“…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]. After more than 20 years exploring the role of Dpp as a tissue organizer, our studies have now uncovered another key role for Dpp, required for hormone-mediated autophagy-dependent midgut removal.…”

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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“…49 The Mad/ Medea complex has been shown to target activation regulatory elements in response to DPP, 50 as well as repressive regulatory elements to which the transcriptional repressor Schnurri is recruited. 51,52 The expression of several genes depends on Activin signaling components, [53][54][55] but dSmad2 regulatory elements have not been identified. Therefore, in order to effectively capture the chromatin landscape of TGF-b signaling pathways, we carried out ChIP-seq experiments against dSmad2, Mad, Medea, and Schnurri in the late-embryonic Drosophila hemocyte cell line Kc167 (Fig.…”

Section: Resultsmentioning

confidence: 99%

CTCF-dependent co-localization of canonical Smad signaling factors at architectural protein binding sites in D. melanogaster

et al. 2015

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The transforming growth factor b (TGF-b) and bone morphogenetic protein (BMP) pathways transduce extracellular signals into tissue-specific transcriptional responses. During this process, signaling effector Smad proteins translocate into the nucleus to direct changes in transcription, but how and where they localize to DNA remain important questions. We have mapped Drosophila TGF-b signaling factors Mad, dSmad2, Medea, and Schnurri genome-wide in Kc cells and find that numerous sites for these factors overlap with the architectural protein CTCF. Depletion of CTCF by RNAi results in the disappearance of a subset of Smad sites, suggesting Smad proteins localize to CTCF binding sites in a CTCF-dependent manner. Sensitive Smad binding sites are enriched at low occupancy CTCF peaks within topological domains, rather than at the physical domain boundaries where CTCF may function as an insulator. In response to Decapentaplegic, CTCF binding is not significantly altered, whereas Mad, Medea, and Schnurri are redirected from CTCF to non-CTCF binding sites. These results suggest that CTCF participates in the recruitment of Smad proteins to a subset of genomic sites and in the redistribution of these proteins in response to BMP signaling.

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“…However, adult D. melanogaster lacking enteroendocrine cells still make and secrete digestive enzymes albeit at a reduced level, and are viable and feed and reproduce normally [38 ]. Indeed, production of lipases and carbohydrases is to a large extent controlled by the fat body through the secretion of the transforming growth factor b ligand, Dawdle [39]. The activity of NPF on male Malpighian tubules indicates a sex-specific role for an EP [27] which obviously is hormonally released as neuronal NPF is confined to interneurons [40].…”

Section: Functions Of Insect Epsmentioning

confidence: 98%

Chemical identity, function and regulation of enteroendocrine peptides in insects

Wegener

Veenstra

2015

Current Opinion in Insect Science

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Transforming Growth Factor β/Activin Signaling Functions as a Sugar-Sensing Feedback Loop to Regulate Digestive Enzyme Expression

Cited by 90 publications

References 50 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

CTCF-dependent co-localization of canonical Smad signaling factors at architectural protein binding sites in D. melanogaster

Chemical identity, function and regulation of enteroendocrine peptides in insects

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