Enteroendocrine cell expression of split-GAL4 drivers bearing regulatory sequences associated with panneuronally expressed genes in Drosophila melanogaster

Holsopple, Jessica M; Cook, Kevin R.; Popodi, Ellen

doi:10.17912/micropub.biology.000628

Cited by 3 publications

(3 citation statements)

References 7 publications

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“…Note that pan-neuronal drivers, including elav-GAL4 and nSyb-GAL4 , are expressed at low levels in EEs (Holsopple et al, 2022a, 2022b; Katheder et al, 2023), consistent with our findings that nSyb transcripts are at lower levels in EEs than neurons (fig. S19A).…”

Section: Resultssupporting

confidence: 91%

Whole organism snRNA-seq reveals systemic peripheral changes in Alzheimer’s Disease fly models

Park,

Lu,

Jackson

et al. 2024

Preprint

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Peripheral tissues become disrupted in Alzheimer's Disease (AD). However, a comprehensive understanding of how the expression of AD-associated toxic proteins, Aβ42 and Tau, in neurons impacts the periphery is lacking. Using Drosophila, a prime model organism for studying aging and neurodegeneration, we generated the Alzheimer's Disease Fly Cell Atlas (AD-FCA): whole-organism single-nucleus transcriptomes of 219 cell types from adult flies neuronally expressing human Aβ42 or Tau. In-depth analyses and functional data reveal impacts on peripheral sensory neurons by Aβ42 and on various non-neuronal peripheral tissues by Tau, including the gut, fat body, and reproductive system. This novel AD atlas provides valuable insights into potential biomarkers and the intricate interplay between the nervous system and peripheral tissues in response to AD-associated proteins.

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Section: Resultssupporting

confidence: 91%

Whole organism snRNA-seq reveals systemic peripheral changes in Alzheimer’s Disease fly models

Park,

Lu,

Jackson

et al. 2024

Preprint

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“…To demonstrate the role of EECs in AA-sensing, EEC-specific manipulations without affecting the development or function of other cells, in particular neurons, are highly demanding. Because EEC specification shares a common root with that of sensory neurons 46 and most EECderived neuropeptide hormones are also produced in the brain [54][55][56] , none of the available Gal4 drivers allows for EEC-specific manipulations 58,59 . Tachykinin (gut)-Gal4 (Tkg-Gal4) was reported to be specific to TK + EECs 60 , and has been used in a number of intestinal studies [61][62][63][64][65][66] .…”

Section: Loss Of Eecs Increases Food Intakementioning

confidence: 99%

“…In addition, a Gal80 transgene driven by an enhancer fragment (R57C10) of neuronal Synaptobrevin (nSyb) is often used in combination with Gal4 drivers to suppress Gal4 transcriptional activity in CNS, with the expectation that only EECs are manipulated 68,69 . However, the R57C10 fragment is also active in EECs 58,70 . An attempt has been made to ablate EECs by knocking down a proneural factor Scute (Sc) using the intestinal progenitor driver, esg-Gal4 61 .…”

Section: Loss Of Eecs Increases Food Intakementioning

confidence: 99%

Dietary L-Glu sensing by enteroendocrine cells adjusts food intake via modulating gut PYY/NPF secretion

Gao,

Zhang,

Deng

et al. 2024

Nat Commun

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Amino acid availability is monitored by animals to adapt to their nutritional environment. Beyond gustatory receptors and systemic amino acid sensors, enteroendocrine cells (EECs) are believed to directly percept dietary amino acids and secrete regulatory peptides. However, the cellular machinery underlying amino acid-sensing by EECs and how EEC-derived hormones modulate feeding behavior remain elusive. Here, by developing tools to specifically manipulate EECs, we find that Drosophila neuropeptide F (NPF) from mated female EECs inhibits feeding, similar to human PYY. Mechanistically, dietary L-Glutamate acts through the metabotropic glutamate receptor mGluR to decelerate calcium oscillations in EECs, thereby causing reduced NPF secretion via dense-core vesicles. Furthermore, two dopaminergic enteric neurons expressing NPFR perceive EEC-derived NPF and relay an anorexigenic signal to the brain. Thus, our findings provide mechanistic insights into how EECs assess food quality and identify a conserved mode of action that explains how gut NPF/PYY modulates food intake.

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Neurofibromin deficiency alters the patterning and prioritization of motor behaviors in a state-dependent manner

Suarez,

Kumar,

Brunner

et al. 2024

Preprint

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Genetic disorders such as neurofibromatosis type 1 increase vulnerability to cognitive and behavioral disorders, such as autism spectrum disorder and attention-deficit/hyperactivity disorder. Neurofibromatosis type 1 results from loss-of-function mutations in the neurofibromin gene and subsequent reduction in the neurofibromin protein (Nf1). While the mechanisms have yet to be fully elucidated, loss of Nf1 may alter neuronal circuit activity leading to changes in behavior and susceptibility to cognitive and behavioral comorbidities. Here we show that mutations decreasing Nf1 expression alter motor behaviors, impacting the patterning, prioritization, and behavioral state dependence in aDrosophilamodel of neurofibromatosis type 1. Loss of Nf1 increases spontaneous grooming in a nonlinear spatial and temporal pattern, differentially increasing grooming of certain body parts, including the abdomen, head, and wings. This increase in grooming could be overridden by hunger in food-deprived foraging animals, demonstrating that the Nf1 effect is plastic and internal state-dependent. Stimulus-evoked grooming patterns were altered as well, withnf1mutants exhibiting reductions in wing grooming when coated with dust, suggesting that hierarchical recruitment of grooming command circuits was altered. Yet loss of Nf1 in sensory neurons and/or grooming command neurons did not alter grooming frequency, suggesting that Nf1 affects grooming via higher-order circuit alterations. Changes in grooming coincided with alterations in walking. Flies lacking Nf1 walked with increased forward velocity on a spherical treadmill, yet there was no detectable change in leg kinematics or gait. Thus, loss of Nf1 alters motor function without affecting overall motor coordination, in contrast to other genetic disorders that impair coordination. Overall, these results demonstrate that loss of Nf1 alters the patterning and prioritization of repetitive behaviors, in a state-dependent manner, without affecting motor coordination.

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Enteroendocrine cell expression of split-GAL4 drivers bearing regulatory sequences associated with panneuronally expressed genes in Drosophila melanogaster

Cited by 3 publications

References 7 publications

Whole organism snRNA-seq reveals systemic peripheral changes in Alzheimer’s Disease fly models

Whole organism snRNA-seq reveals systemic peripheral changes in Alzheimer’s Disease fly models

Dietary L-Glu sensing by enteroendocrine cells adjusts food intake via modulating gut PYY/NPF secretion

Neurofibromin deficiency alters the patterning and prioritization of motor behaviors in a state-dependent manner

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