Defective cortex glia plasma membrane structure underlies light-induced epilepsy in cpes mutants

Proceedings of the National Academy of Sciences, Год журнала: 2018, Номер 115(38)

Опубликована: Сен. 5, 2018

Seizures induced by visual stimulation (photosensitive epilepsy; PSE) represent a common type of epilepsy in humans, but the molecular mechanisms and genetic drivers underlying PSE remain unknown, no good animal models have been identified as yet. Here, we show an model PSE, Drosophila, owing to defective cortex glia. The glial membranes are severely compromised ceramide phosphoethanolamine synthase (cpes)-null mutants fail encapsulate neuronal cell bodies Drosophila cortex. Expression human sphingomyelin 1, which synthesizes closely related phosphocholine (sphingomyelin), rescues abnormalities underscoring evolutionarily conserved role these lipids membranes. Further, compromise plasma membrane structure that underlies collapse cpes leads phenotype.

Язык: Английский

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Pvr receptor tyrosine kinase signaling promotes post-embryonic morphogenesis, and survival of glia and neural progenitor cells in Drosophila

Development, Год журнала: 2018, Номер 145(23)

Опубликована: Окт. 16, 2018

Stem cells reside in specialized microenvironments, called niches, that regulate their development and the of progeny. However, maintenance niches are poorly understood. In Drosophila brain, cortex glial provide a niche promotes self-renewal proliferation neural stem cell-like (neuroblasts). central neuroblasts progeny control post-embryonic morphogenesis glia through PDGF-like ligands, this PDGFR receptor tyrosine kinase (RTK) signaling is required for expression DE-cadherin, which sustains neuroblasts. Thus, an RTK-dependent feed-forward loop, actively maintain each other. When EGFR RTK constitutively activated glia, they overexpress PDGF orthologs to stimulate autocrine signaling, uncouples growth survival from neuroblasts, drives neoplastic transformation elimination These results fundamental insights into regulation, show niche-neural cell becomes hijacked drive tumorigenesis.

Язык: Английский

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Glial Hedgehog signalling and lipid metabolism regulate neural stem cell proliferation in Drosophila

EMBO Reports, Год журнала: 2021, Номер 22(5)

Опубликована: Март 10, 2021

Язык: Английский

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Redundant functions of the SLC5A transporters Rumpel, Bumpel, and Kumpel in ensheathing glial cells

Biology Open, Год журнала: 2021, Номер 11(1)

Опубликована: Дек. 13, 2021

Neuronal processing is energy demanding and relies on sugar metabolism. To nurture the Drosophila nervous system, blood-brain barrier forming glial cells take up trehalose from hemolymph then distribute metabolic products further to all neurons. This function provided by glucose lactate transporters of solute carrier (SLC) 5A family. Here we identified three SLC5A genes that are specifically expressed in overlapping sets CNS cells, rumpel, bumpel kumpel. We generated mutants viable fertile, lacking discernible phenotypes. Loss rumpel causes subtle locomotor phenotypes flies display increased daytime sleep. In addition, kumpel double mutants, an even greater extent triple oogenesis disrupted at onset vitollegenic phase. indicates a partially redundant between these genes. Rescue experiments exploring this effect indicate can be affected cells. Moreover, expression heterologous mammalian transporters, with known transport properties, suggest Bumpel and/or Kumpel or lactate. Overall, our results imply redundancy nutrient sensing functions affecting ovarian development behavior.

Язык: Английский

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An interplay between cellular growth and atypical fusion defines morphogenesis of a modular glial niche in Drosophila

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Авг. 25, 2022

Abstract Neural stem cells (NSCs) live in an intricate cellular microenvironment supporting their activity, the niche. Whilst shape and function are inseparable, morphogenetic aspects of niche development poorly understood. Here, we use formation a glial to investigate acquisition architectural complexity. Cortex glia (CG) Drosophila regulate neurogenesis build reticular structure around NSCs. We first show that individual CG grow tremendously ensheath several NSC lineages, employing elaborate proliferative mechanisms which convert these into syncytia rich cytoplasmic bridges. further undergo homotypic cell–cell fusion, using defined cell surface receptors actin regulators. Cellular exchange is however dynamic space time. This atypical fusion remodels borders, restructuring syncytia. Ultimately, combined growth builds multi-level architecture niche, creates modular, spatial partition population. Our findings provide insights how forms organises while developing intimate contacts with

Язык: Английский

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Insulin signaling in development

Development, Год журнала: 2023, Номер 150(20)

Опубликована: Окт. 15, 2023

ABSTRACT Nutrient intake is obligatory for animal growth and development, but nutrients alone are not sufficient. Indeed, insulin homologous hormones required normal even in the presence of nutrients. These communicate nutrient status between organs, allowing animals to coordinate metabolism with supply. Insulin related hormones, such as insulin-like factors peptides, play important roles development metabolism, defects production signaling leading hyperglycemia diabetes. Here, we describe hormone family signal transduction pathways activated by these hormones. We highlight coordinating maternal fetal during pregnancy, how secretion regulated at different life stages. Additionally, discuss cell growth, stem proliferation differentiation. provide examples role across multiple model organisms: Caenorhabditis elegans, Drosophila, zebrafish, mouse human.

Язык: Английский

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Hsp83/Hsp90 Physically Associates with Insulin Receptor to Promote Neural Stem Cell Reactivation

Stem Cell Reports, Год журнала: 2018, Номер 11(4), С. 883 - 896

Опубликована: Сен. 20, 2018

Neural stem cells (NSCs) have the ability to exit quiescence and reactivate in response physiological stimuli. In Drosophila brain, insulin receptor (InR)/phosphatidylinositol 3-kinase (PI3K)/Akt pathway triggers NSC reactivation. However, intrinsic mechanisms that control InR/PI3K/Akt during reactivation remain unknown. Here, we identified heat shock protein 83 (Hsp83/Hsp90), a molecular chaperone, as an regulator of Hsp83 is both necessary sufficient for by promoting activation InR larval brains presence dietary amino acids. Both its co-chaperone Cdc37 physically associate with InR. Finally, defects observed depleted hsp83 were rescued over-activation pathway, suggesting functions upstream Given conservation our finding may provide insights into underlying mammalian

Язык: Английский

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Sexual dimorphism of niche architecture and regulation of theCaenorhabditis elegansgermline stem cell pool

Molecular Biology of the Cell, Год журнала: 2019, Номер 30(14), С. 1757 - 1769

Опубликована: Май 8, 2019

Stem cell maintenance by niche signaling is a common theme across phylogeny. In the Caenorhabditis elegans gonad, broad outlines of germline stem (GSC) regulation are same for both sexes: GLP-1/Notch from mesenchymal distal tip maintains GSCs in gonad sexes and does so via two key regulators, SYGL-1 LST-1. Yet most recent analyses GSC have focused on XX hermaphrodites, an essentially female sex making sperm larvae oocytes adults. Here we focus XO males. Sexual dimorphism architecture, reported previously, suggested that molecular responses to or numbers might also be sexually distinct. Remarkably, this not case. This work extends our understanding dimorphic but demonstrates niches drive similar response maintain number their pools.

Язык: Английский

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CRL4Mahj E3 ubiquitin ligase promotes neural stem cell reactivation

PLoS Biology, Год журнала: 2019, Номер 17(6), С. e3000276 - e3000276

Опубликована: Июнь 6, 2019

The ability of neural stem cells (NSCs) to transit between quiescence and proliferation is crucial for brain development homeostasis. Drosophila Hippo pathway maintains NSC quiescence, but its regulation during remains unknown. Here, we show that CRL4Mahj, an evolutionarily conserved E3 ubiquitin ligase, essential reactivation (exit from quiescence). We demonstrate damaged DNA-binding protein 1 (DDB1) Cullin4, two core components Cullin4-RING ligase (CRL4), are intrinsically required reactivation. have identified a substrate receptor CRL4, Mahjong (Mahj), which necessary sufficient Moreover, CRL4Mahj forms complex with Warts (Wts/large tumor suppressor [Lats]), kinase the signaling pathway, Mahj promotes ubiquitination Wts. Our genetic analyses further support conclusion triggers by inhibition Given Cullin4B mutations cause mental retardation cerebral malformation, similar regulatory mechanisms may be applied human brain.

Язык: Английский

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Notch signaling regulates neural stem cell quiescence entry and exit in Drosophila

Development, Год журнала: 2022, Номер 149(4)

Опубликована: Фев. 3, 2022

Stem cells enter and exit quiescence as part of normal developmental programs to maintain tissue homeostasis in adulthood. Although it is clear that stem cell intrinsic extrinsic cues, local systemic, regulate quiescence, remains unclear whether cues coordinate control how cue coordination achieved. Here, we report Notch signaling coordinates neuroblast temporal with nutrient Drosophila. When activity reduced, delayed or altogether bypassed, some neuroblasts dividing continuously during the embryonic-to-larval transition. During embryogenesis before express ligand Delta. After division, Delta partitioned adjacent GMC daughters where transactivates neuroblasts. Over time, response increasing numbers Delta-expressing daughters, increases, leading cycle consequently, attenuation pathway activity. Quiescent have low no active Notch, which required for from cues. Thus, proliferation versus decisions.

Язык: Английский

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