Selection of Motor Programs for Suppressing Food Intake and Inducing Locomotion in the Drosophila Brain

Schoofs, Andreas; Hückesfeld, Sebastian; Schlegel, Philipp; Miroschnikow, Anton; Peters, Marc; Zeymer, Malou; Spieß, Roland; Chiang, Ann‐Shyn; Pankratz, Michael J.

doi:10.1371/journal.pbio.1001893

Cited by 82 publications

(125 citation statements)

References 86 publications

(95 reference statements)

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“…In rodents, NMU signaling may be a central regulator of satiety and feeding behavior (Hanada et al, 2004; Howard et al, 2000), and this role may be conserved in other organisms (Pang and Curran, 2014; Schoofs et al, 2014). In addition, NMU mutant mice have increased adiposity and hyperinsulinemia (Hanada et al 2004), but a direct role for NMU in regulating insulin secretion by insulin-producing cells was not identified.…”

Section: Discussionmentioning

confidence: 99%

Suppression of Insulin Production and Secretion by a Decretin Hormone

et al. 2015

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SUMMARY Decretins, hormones induced by fasting that suppress insulin production and secretion, have been postulated from classical human metabolic studies. From genetic screens, we identified Drosophila Limostatin (Lst), a peptide hormone that suppresses insulin secretion. Lst is induced by nutrient restriction in gut-associated endocrine cells. limostatin deficiency led to hyperinsulinemia, hypoglycemia and excess adiposity. A conserved 15-residue polypeptide encoded by limostatin suppressed secretion by insulin-producing cells. Targeted knockdown of CG9918, a Drosophila orthologue of Neuromedin U receptors (NMUR), in insulin-producing cells phenocopied limostatin deficiency, and attenuated insulin suppression by purified Lst, suggesting CG9918 encodes an Lst receptor. NMUR1 is expressed in islet β-cells, and purified NMU suppresses insulin secretion from human islets. A human mutant NMU variant that co-segregates with familial early-onset obesity and hyperinsulinemia fails to suppress insulin secretion. We propose Lst as an index member of an ancient hormone class called decretins, which suppress insulin output.

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Section: Discussionmentioning

confidence: 99%

Suppression of Insulin Production and Secretion by a Decretin Hormone

et al. 2015

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“…Although some progress has been made on understanding the relationship of locomotion to feeding (Mann et al 2013, Schoofs et al 2014, it will be interesting to determine the neural architecture that allows the same gustatory and satiety signals to control motor outputs for both the proboscis and the legs differentially.…”

Section: Resultsmentioning

confidence: 99%

“…Peptidergic hugin neurons have arbors in the SEZ in close proximity to bitter receptor terminals (Bader et al 2007), and, when silenced, cause flies to spend less time evaluating novel food before eating (Melcher and Pankratz 2005). In larvae, activation of hugin neurons both suppresses feeding and induces a motor program for locomotion (Schoofs et al 2014).…”

Section: Interneuronsmentioning

confidence: 99%

Motor control of fly feeding

McKellar¹

2016

Journal of Neurogenetics

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Following considerable progress on the molecular and cellular basis of taste perception in fly sensory neurons, the time is now ripe to explore how taste information, integrated with hunger and satiety, undergo a sensorimotor transformation to lead to the motor actions of feeding behavior. I examine what is known of feeding circuitry in adult flies from more than 250 years of work in larger flies and from newer work in Drosophila. I review the anatomy of the proboscis, its muscles and their functions (where known), its motor neurons, interneurons known to receive taste inputs, interneurons that diverge from taste circuitry to provide information to other circuits, interneurons from other circuits that converge on feeding circuits, proprioceptors that influence the motor control of feeding, and sites of integration of hunger and satiety on feeding circuits. In spite of the several neuron types now known, a connected pathway from taste inputs to feeding motor outputs has yet to be found. We are on the threshold of an era where these individual components will be assembled into circuits, revealing how nervous system architecture leads to the control of behavior.

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“…Alternatively, foraging may be functioning acutely during the behavior to elicit its phenotypic effects. hugin neurons, or their targets, are candidate cells for foraging function since acute manipulation of these cells can alter larval locomotion and feeding (Schoofs et al 2014). A lack of foraging in D. melanogaster could also affect larval path length or feeding due to altered muscle function, making the muscles less sensitive to incoming neuronal stimuli.…”

Section: Discussionmentioning

confidence: 99%

Feeding-Related Traits Are Affected by Dosage of theforagingGene inDrosophila melanogaster

et al. 2017

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Nutrient acquisition and energy storage are critical parts of achieving metabolic homeostasis. The foraging gene in Drosophila melanogaster has previously been implicated in multiple feeding-related and metabolic traits. Before foraging's functions can be further dissected, we need a precise genetic null mutant to definitively map its amorphic phenotypes. We used homologous recombination to precisely delete foraging, generating the for 0 null allele, and used recombineering to reintegrate a full copy of the gene, generating the {for BAC } rescue allele. We show that a total loss of foraging expression in larvae results in reduced larval path length and food intake behavior, while conversely showing an increase in triglyceride levels. Furthermore, varying foraging gene dosage demonstrates a linear dose-response on these phenotypes in relation to foraging gene expression levels. These experiments have unequivocally proven a causal, dose-dependent relationship between the foraging gene and its pleiotropic influence on these feeding-related traits. Our analysis of foraging's transcription start sites, termination sites, and splicing patterns using rapid amplification of cDNA ends (RACE) and full-length cDNA sequencing, revealed four independent promoters, pr1-4, that produce 21 transcripts with nine distinct open reading frames (ORFs). The use of alternative promoters and alternative splicing at the foraging locus creates diversity and flexibility in the regulation of gene expression, and ultimately function. Future studies will exploit these genetic tools to precisely dissect the isoform-and tissue-specific requirements of foraging's functions and shed light on the genetic control of feeding-related traits involved in energy homeostasis.

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Selection of Motor Programs for Suppressing Food Intake and Inducing Locomotion in the Drosophila Brain

Abstract: This study reveals that a cluster of neurons expressing the neuropeptide hugin transmit inputs from higher brain centers to motor centers, thereby regulating feeding and locomotion in fruit fly larvae.

Cited by 82 publications

References 86 publications

Suppression of Insulin Production and Secretion by a Decretin Hormone

Suppression of Insulin Production and Secretion by a Decretin Hormone

Motor control of fly feeding

Feeding-Related Traits Are Affected by Dosage of theforagingGene inDrosophila melanogaster

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