Abstract:The digestive system is gaining interest as a major regulator of various functions including immune defense, nutrient accumulation, and regulation of feeding behavior, aside from its conventional function as a digestive organ. The Drosophila midgut epithelium is completely renewed every 1–2 weeks due to differentiation of pluripotent intestinal stem cells in the midgut. Intestinal stem cells constantly divide and differentiate into enterocytes that secrete digestive enzymes and absorb nutrients, or enteroendoc… Show more
“…First, to unambiguously assess the main source of Bursα production during adulthood, we compared mRNA expression levels in mature whole adults, adult midguts, and adult animals from which the gut was removed prior to RNA extraction (“gut-less”). Confirming our previous results ( Scopelliti et al., 2014 , Scopelliti et al., 2016 ) and subsequent independent reports ( Chen et al., 2016 , Dutta et al., 2015 ), we observed strong enrichment of bursα transcripts in adult midguts ( Figure 1 A). Figure 1 Bursα in ee Cells Is Regulated by Nutrients (A and C) Transcript levels of bursα relative to rpl32 in indicated tissue samples from 10- to 14-day-old adult wild-type animals (A) or whole midguts from animals of the indicated genotypes (C).…”
SummaryThe control of systemic metabolic homeostasis involves complex inter-tissue programs that coordinate energy production, storage, and consumption, to maintain organismal fitness upon environmental challenges. The mechanisms driving such programs are largely unknown. Here, we show that enteroendocrine cells in the adult Drosophila intestine respond to nutrients by secreting the hormone Bursicon α, which signals via its neuronal receptor DLgr2. Bursicon α/DLgr2 regulate energy metabolism through a neuronal relay leading to the restriction of glucagon-like, adipokinetic hormone (AKH) production by the corpora cardiaca and subsequent modulation of AKH receptor signaling within the adipose tissue. Impaired Bursicon α/DLgr2 signaling leads to exacerbated glucose oxidation and depletion of energy stores with consequent reduced organismal resistance to nutrient restrictive conditions. Altogether, our work reveals an intestinal/neuronal/adipose tissue inter-organ communication network that is essential to restrict the use of energy and that may provide insights into the physiopathology of endocrine-regulated metabolic homeostasis.
“…First, to unambiguously assess the main source of Bursα production during adulthood, we compared mRNA expression levels in mature whole adults, adult midguts, and adult animals from which the gut was removed prior to RNA extraction (“gut-less”). Confirming our previous results ( Scopelliti et al., 2014 , Scopelliti et al., 2016 ) and subsequent independent reports ( Chen et al., 2016 , Dutta et al., 2015 ), we observed strong enrichment of bursα transcripts in adult midguts ( Figure 1 A). Figure 1 Bursα in ee Cells Is Regulated by Nutrients (A and C) Transcript levels of bursα relative to rpl32 in indicated tissue samples from 10- to 14-day-old adult wild-type animals (A) or whole midguts from animals of the indicated genotypes (C).…”
SummaryThe control of systemic metabolic homeostasis involves complex inter-tissue programs that coordinate energy production, storage, and consumption, to maintain organismal fitness upon environmental challenges. The mechanisms driving such programs are largely unknown. Here, we show that enteroendocrine cells in the adult Drosophila intestine respond to nutrients by secreting the hormone Bursicon α, which signals via its neuronal receptor DLgr2. Bursicon α/DLgr2 regulate energy metabolism through a neuronal relay leading to the restriction of glucagon-like, adipokinetic hormone (AKH) production by the corpora cardiaca and subsequent modulation of AKH receptor signaling within the adipose tissue. Impaired Bursicon α/DLgr2 signaling leads to exacerbated glucose oxidation and depletion of energy stores with consequent reduced organismal resistance to nutrient restrictive conditions. Altogether, our work reveals an intestinal/neuronal/adipose tissue inter-organ communication network that is essential to restrict the use of energy and that may provide insights into the physiopathology of endocrine-regulated metabolic homeostasis.
“…Second, DH31 has been implicated in the control of visceral muscle peristalsis and motility in Drosophila larvae [ 33 , 34 ]. Third, although DH31 is expressed in many EECs located in the posterior adult midgut, the expression of DH31 has been detected in few anterior EECs in the adult midgut [ 35 , 36 ]. Fourth, two transcriptomic analyses in the Drosophila midgut revealed that the DH31 receptor-encoding gene (DH31-R ) [ 37 ] is expressed in the anterior region of visceral muscle [ 38 , 39 ] ( http://flygut.epfl.ch ; http://flygutseq.buchonlab.com ).…”
The digestive tract is the first organ affected by the ingestion of foodborne bacteria. While commensal bacteria become resident, opportunistic or virulent bacteria are eliminated from the gut by the local innate immune system. Here we characterize a new mechanism of defense, independent of the immune system, in Drosophila melanogaster. We observed strong contractions of longitudinal visceral muscle fibers for the first 2 hours following bacterial ingestion. We showed that these visceral muscle contractions are induced by immune reactive oxygen species (ROS) that accumulate in the lumen and depend on the ROS-sensing TRPA1 receptor. We then demonstrate that both ROS and TRPA1 are required in a subset of anterior enteroendocrine cells for the release of the DH31 neuropeptide which activates its receptor in the neighboring visceral muscles. The resulting contractions of the visceral muscles favors quick expulsion of the bacteria, limiting their presence in the gut. Our results unveil a precocious mechanism of defense against ingested opportunistic bacteria, whether they are Gram-positive like Bacillus thuringiensis or Gram-negative like Erwinia carotovora carotovora. Finally, we found that the human homolog of DH31, CGRP, has a conserved function in Drosophila.
“…Additionally DILP3 is produced by intestinal muscle cells ( Veenstra et al, 2008 ) and sparse bursicon expression was seen in some EECs ( Scopelliti et al, 2014 ). In EECs of the anterior and middle midgut TK and NPF are colocalized, in the midportion orcokinin B and allatostatin C, and in the posterior end TK and DH31 ( Figure 9A ) ( Veenstra et al, 2008 ; Veenstra and Ida, 2014 ; Chen et al, 2016a ). Of note is that in the larval gut anteriorly located MIP producing EECs were shown to also express Cha, suggesting that they produce acetylcholine, which may act in paracrine signaling ( LaJeunesse et al, 2010 ).…”
Section: Colocalization Of Peptides In Intestinal Endocrine Cellsmentioning
It has been known for more than 40 years that individual neurons can produce more than one neurotransmitter and that neuropeptides often are colocalized with small molecule neurotransmitters (SMNs). Over the years much progress has been made in understanding the functional consequences of cotransmission in the nervous system of mammals. There are also some excellent invertebrate models that have revealed roles of coexpressed neuropeptides and SMNs in increasing complexity, flexibility, and dynamics in neuronal signaling. However, for the fly Drosophila there are surprisingly few functional studies on cotransmission, although there is ample evidence for colocalization of neuroactive compounds in neurons of the CNS, based both on traditional techniques and novel single cell transcriptome analysis. With the hope to trigger interest in initiating cotransmission studies, this review summarizes what is known about Drosophila neurons and neuronal circuits where different neuropeptides and SMNs are colocalized. Coexistence of neuroactive substances has been recorded in different neuron types such as neuroendocrine cells, interneurons, sensory cells and motor neurons. Some of the circuits highlighted here are well established in the analysis of learning and memory, circadian clock networks regulating rhythmic activity and sleep, as well as neurons and neuroendocrine cells regulating olfaction, nociception, feeding, metabolic homeostasis, diuretic functions, reproduction, and developmental processes. One emerging trait is the broad role of short neuropeptide F in cotransmission and presynaptic facilitation in a number of different neuronal circuits. This review also discusses the functional relevance of coexisting peptides in the intestine. Based on recent single cell transcriptomics data, it is likely that the neuronal systems discussed in this review are just a fraction of the total set of circuits where cotransmission occurs in Drosophila. Thus, a systematic search for colocalized neuroactive compounds in further neurons in anatomically defined circuits is of interest for the near future.
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