The IGFBP7 homolog Imp-L2 promotes insulin signaling in distinct neurons of the <i>Drosophila</i> brain

Bader, R.; Sarraf-Zadeh, Ladan; Peters, Marc; Moderau, Nina; Stocker, Hugo; Köhler, Katja; Pankratz, Michael J.; Hafen, Ernst

doi:10.1242/dev.100065

Cited by 16 publications

(20 citation statements)

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“…and thereby regulate metabolism-associated activity and sleep [2]. The signaling between IPCs and ITPn seem to be by DILP2 (see [59]) or and to other brain neurons possibly by colocalized classical neurotransmitters (CT). The LHLKs may regulate IPCs, which in turn activate ITPn and thereby affect central (sNPF and TK) and peripheral signaling (DILPs and ITP).…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Neuropeptides in modulation of Drosophila behavior: how to get a grip on their pleiotropic actions

Nässel

Pauls

Huetteroth

2019

Preprint

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Neuropeptides constitute a large and diverse class of signaling molecules that are produced by many types of neurons, neurosecretory cells, endocrines and other cells. Many neuropeptides display pleiotropic actions either as neuromodulators, co-transmitters or circulating hormones, while some play these roles concurrently. Here, we highlight pleiotropic functions of neuropeptides and different levels of neuropeptide signaling in the brain, from context-dependent orchestrating signaling by higher order neurons, to local executive modulation in specific circuits. Additionally, orchestrating neurons receive peptidergic signals from neurons conveying organismal internal state cues and relay these to executive circuits. We exemplify these levels of signaling with four neuropeptides, SIFamide, short neuropeptide F, allatostatin-A and leucokinin, each with a specific expression pattern and level of complexity in signaling.

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Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Neuropeptides in modulation of Drosophila behavior: how to get a grip on their pleiotropic actions

Nässel

Pauls

Huetteroth

2019

Preprint

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“…For antibody stainings of CG8784-6kb-GAL4, larvae expressing 10XUAS-mCD8::GFP (Bloomington, #32184) driven by CG8784-6kb-GAL4 were dissected in PBS. Brains were fixed in 4% paraformaldehyde for 30 minutes, rinsed, blocked in 5% normal goat serum, and incubated overnight at 4°C with primaries: goat anti-GFP-FITC (abcam, ab26662), 1:500; rabbit anti-DH44 [90] (gift of Jan Veenstra), 1:1000; guinea pig anti-Dilp2 [103] (Pankratz lab), 1:500 and rabbit anti-DMS [56,102] (gift of Luc van den Bosch and Liliane Schoofs), 1:500. Tissues were rinsed and incubated overnight at 4°C in secondaries: anti-rabbit Alexa Fluor 633 (Invitrogen, A-21070) and anti-guinea pig Alexa Fluor 568 (Invitrogen, A-11075), both 1:500.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Synaptic Transmission Parallels Neuromodulation in a Central Food-Intake Circuit

Schlegel

Texada

Miroschnikow

et al. 2016

Preprint

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NeuromedinU is a potent regulator of food intake and activity in mammals. In Drosophila, neurons producing the homologous neuropeptide hugin regulate feeding and locomotion in a similar manner. Here, we use EM-based reconstruction to generate the entire connectome of hugin-producing neurons in the Drosophila larval CNS. We demonstrate that hugin neurons use synaptic transmission in addition to peptidergic neuromodulation and identify acetylcholine as a key transmitter. Hugin neuropeptide and acetylcholine are both necessary for the regulatory effect on feeding. We further show that subtypes of hugin neurons connect chemosensory to endocrine system by combinations of synaptic and peptide-receptor connections. Targets include endocrine neurons producing DH44, a CRH-like peptide, and insulin-like peptides. Homologs of these peptides are likewise downstream of neuromedinU, revealing striking parallels in flies and mammals. We propose that hugin neurons are part of an ancient physiological control system that has been conserved at functional and molecular level.

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“…Flies deficient in Imp-L2 are larger in size and more vulnerable to starvation than wild-type flies (8), whereas increased expression of Imp-L2 extends the fly lifespan (11,12). Moreover, Imp-L2 expressed in a subset of neurons ensures the proper activity of insulin signaling in the brain and its associated glands (13,14). Other recent studies have further revealed the role of Imp-L2 in cachexia-like syndromes, where malignant tumors induce organ wasting (15,16).…”

mentioning

confidence: 99%

Steroid signaling mediates nutritional regulation of juvenile body growth via IGF-binding protein in Drosophila

Lee

Han

Yun

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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Nutritional condition during the juvenile growth period considerably affects final adult size. The insulin/insulin-like growth factor signaling (IIS)/target of rapamycin (TOR) nutrient-sensing pathway is known to regulate growth and metabolism in response to nutritional conditions. However, there is limited information on how endocrine pathways communicate nutritional information to different metabolic organs to regulate organismal growth. Here, we show that Imaginal morphogenesis protein-Late 2 (Imp-L2), a homolog of insulin-like growth factor-binding protein 7 (IGFBP7), plays a key role in the nutritional control of organismal growth. Nutritional restriction during the larval growth period causes undersized adults, which is largely diminished by mutation. We delineate a pathway in which nutritional restriction increases levels of the steroid hormone ecdysone, which, in turn, triggers ecdysone signaling-dependent Imp-L2 production from the fat body, a fly adipose organ, thereby attenuating peripheral IIS and body growth. Surprisingly, this endocrine pathway operates independent of the fat-body-TOR internal nutrient sensor, long believed to be the control center for nutrition-dependent growth. Our study reveals a previously unrecognized endocrine circuit mediating nutrition-dependent juvenile growth, which could also potentially be related to the insulin resistance frequently observed in puberty.

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The IGFBP7 homolog Imp-L2 promotes insulin signaling in distinct neurons of the Drosophila brain

Cited by 16 publications

References 1 publication

Neuropeptides in modulation of Drosophila behavior: how to get a grip on their pleiotropic actions

Neuropeptides in modulation of Drosophila behavior: how to get a grip on their pleiotropic actions

Synaptic Transmission Parallels Neuromodulation in a Central Food-Intake Circuit

Steroid signaling mediates nutritional regulation of juvenile body growth via IGF-binding protein in Drosophila

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