FOXO1-mediated lipid metabolism maintains mammalian embryos in dormancy

Nature Cell Biology, Journal Year: 2024, Volume and Issue: 26(2), P. 181 - 193

Published: Jan. 4, 2024

Abstract Mammalian developmental timing is adjustable in vivo by preserving pre-implantation embryos a dormant state called diapause. Inhibition of the growth regulator mTOR (mTORi) pauses mouse development vitro, yet how embryonic dormancy maintained not known. Here we show that diapause are sustained using lipids as primary energy source. In supplementation with metabolite l -carnitine balances lipid consumption, puts deeper and boosts embryo longevity. We identify FOXO1 an essential balance propose, through meta-analyses cell signatures, it may be common across adult tissues. Our results lift constraint on vitro survival suggest metabolism critical metabolic transition relevant for longevity stem function

Language: Английский

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Functions of Stress-Induced Lipid Droplets in the Nervous System

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 10

Published: April 14, 2022

Lipid droplets are highly dynamic intracellular organelles that store neutral lipids such as cholesteryl esters and triacylglycerols. They have recently emerged key stress response components in many different cell types. the nervous system mostly observed vivo glia, ependymal cells microglia. tend to become more numerous these types can also form neurons a consequence of ageing or stresses involving redox imbalance lipotoxicity. Abundant lipid characteristic feature several neurodegenerative diseases. In this minireview, we take cell-type perspective on recent advances our understanding droplet metabolism neural stem during health disease. We highlight given subfunction, triacylglycerol lipolysis, be physiologically beneficial harmful functions depending upon cellular context. The mechanistic context-dependent is progressing apace, aided by new technologies for probing proteome lipidome with single-cell type precision.

Language: Английский

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A high-sugar diet, but not obesity, reduces female fertility in Drosophila melanogaster

Development, Journal Year: 2023, Volume and Issue: 150(20)

Published: Oct. 5, 2023

ABSTRACT Obesity is linked to reduced fertility in various species, from Drosophila humans. Considering that obesity often induced by changes diet or eating behavior, it remains unclear whether obesity, diet, both reduce fertility. Here, we show females on a high-sugar become rapidly obese and less fertile as result of increased death early germline cysts vitellogenic egg chambers (or follicles). They also have high glycogen, glucose trehalose levels develop insulin resistance their fat bodies (but not ovaries). By contrast, with adipocyte-specific knockdown the anti-obesity genes brummer adipose are but normal Remarkably, supplemented separate source water mostly levels, despite persistent glycogen body resistance. These findings demonstrate affects specific processes oogenesis independently resistance, correlate alone does impair

Language: Английский

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Aging and memory are altered by genetically manipulating lactate dehydrogenase in the neurons or glia of flies

Aging, Journal Year: 2023, Volume and Issue: unknown

Published: Feb. 27, 2023

The astrocyte-neuron lactate shuttle hypothesis posits that glial-generated is transported to neurons fuel metabolic processes required for long-term memory. Although studies in vertebrates have revealed shuttling important cognitive function, it uncertain if this form of coupling conserved invertebrates or influenced by age. Lactate dehydrogenase (Ldh) a rate limiting enzyme interconverts and pyruvate. Here we genetically manipulated expression Drosophila melanogaster (dLdh) glia assess the impact altered metabolism on invertebrate aging courtship memory at different ages. We also assessed survival, negative geotaxis, brain neutral lipids (the core component lipid droplets) metabolites. Both upregulation downregulation dLdh resulted decreased survival impairment with Glial caused age-related without altering while upregulated glial lowered disrupting neuronal increased accumulation. provide evidence age affects tricarboxylic acid (TCA) cycle, 2-hydroxyglutarate (2HG), Collectively, our findings indicate direct alteration either but only an age-dependent manner.

Language: Английский

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

EMBO Reports, Journal Year: 2021, Volume and Issue: 22(5)

Published: March 10, 2021

Language: Английский

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

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Aug. 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

Language: Английский

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The Critical Balance Between Quiescence and Reactivation of Neural Stem Cells

Biomolecules, Journal Year: 2025, Volume and Issue: 15(5), P. 672 - 672

Published: May 6, 2025

Neural stem cells (NSC) are multipotent, self-renewing that give rise to all neural cell types within the central nervous system. During adulthood, most NSCs exist in a quiescent state which can be reactivated response metabolic and signalling changes, allowing for long-term continuous neurogenesis injury. Ensuring critical balance between quiescence reactivation is required maintain limited NSC reservoir replenishment throughout lifetime. The precise mechanisms pathways behind this at focus of current research. In review, we highlight discuss recent studies using Drosophila, mammalian zebrafish models contributing understanding molecular underlying NSCs.

Language: Английский

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Fragile X mental retardation protein coordinates neuron-to-glia communication for clearance of developmentally transient brain neurons

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(12)

Published: March 15, 2023

In the developmental remodeling of brain circuits, neurons are removed by glial phagocytosis to optimize adult behavior. Fragile X mental retardation protein (FMRP) regulates neuron-to-glia signaling drive for targeted neuron pruning. We find that FMRP acts in a mothers against decapentaplegic (Mad)-insulin receptor (InR)-protein kinase B (Akt) pathway regulate pretaporter (Prtp) and amyloid precursor protein-like (APPL) signals directing this clearance. Neuronal RNAi Drosophila fragile 1 ( dfmr1 ) elevates mad transcript levels increases pMad signaling. both elevate phospho–protein (pAkt) delay removal but cause opposite effects on InR expression. Genetically correcting pAkt background restores normal remodeling. Consistently, neuronal decrease Prtp levels, whereas akt increase indicating works with insulin tightly thus control correct circuit all APPL higher endolysosome activity phagocytosis. These findings reveal FMRP-dependent communication pruning, identifying potential molecular mechanisms devising syndrome treatments.

Language: Английский

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Lipid droplets in the nervous system: involvement in cell metabolic homeostasis

Neural Regeneration Research, Journal Year: 2024, Volume and Issue: 20(3), P. 740 - 750

Published: June 11, 2024

Lipid droplets serve as primary storage organelles for neutral lipids in neurons, glial cells, and other cells the nervous system. droplet formation begins with synthesis of endoplasmic reticulum. Previously, lipid were recognized their role maintaining metabolism energy homeostasis; however, recent research has shown that are highly adaptive diverse functions In addition to regulating cell metabolism, play a protective various cellular stress responses. Furthermore, exhibit specific neurons cells. Dysregulation leads dysfunction, metabolic abnormalities, system diseases. This review aims provide an overview system, covering topics such biogenesis, specificity, functions. Additionally, it will explore association between neurodegenerative disorders. Understanding involvement homeostasis related is crucial determine underlying causes exploring potential therapeutic approaches these

Language: Английский

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Differential adhesion during development establishes individual neural stem cell niches and shapes adult behaviour in Drosophila

PLoS Biology, Journal Year: 2023, Volume and Issue: 21(11), P. e3002352 - e3002352

Published: Nov. 9, 2023

Neural stem cells (NSCs) reside in a defined cellular microenvironment, the niche, which supports generation and integration of newborn neurons. The mechanisms building sophisticated niche structure around NSCs their functional relevance for neurogenesis are yet to be understood. In Drosophila larval brain, cortex glia (CG) encase individual NSC lineages membranous chambers, organising cell population neurons into stereotypic structure. We first found that CG wrap lineage-related regardless identity, showing lineage information builds architecture. then discovered mechanism temporally controlled differential adhesion using conserved complexes encasing lineages. An intralineage through homophilic Neuroglian interactions provides strong binding between same lineage, while weaker interaction Neurexin-IV Wrapper exists CG. Loss results clumped together an altered network, loss Neurexin-IV/Wrapper generates larger chamber grouping several together. Axonal projections also these conditions. Further, we link 2 specifically during development locomotor hyperactivity resulting adults. Altogether, our findings identify belt adhesions neurogenic at scale provide proof concept properties shape adult behaviour.

Language: Английский

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