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Updated: Jul 12, 2026
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Real-time Bioluminescence Imaging of Notch Signaling Dynamics during Murine Neurogenesis
Published on: December 12, 2019
Notch Signaling Reprograms Glial Lipid Metabolism to Promote Hypoxia Resistance
Biorxiv : the Preprint Server for Biology
|July 10, 2026
Summary
Glial cells adapt to low oxygen by altering lipid metabolism, a process controlled by Notch signaling. This metabolic rewiring in Eaat1-positive glia enhances brain hypoxia tolerance in developing fruit flies.
Area of Science:
- Neuroscience
- Cell Biology
- Metabolic Research
Background:
- Hypoxia (low oxygen) critically impacts developing nervous systems due to high metabolic needs.
- Glial cells are vital for neural homeostasis during stress, but their metabolic adaptations to hypoxia are unclear.
Purpose of the Study:
- To investigate glial metabolic remodeling for hypoxia tolerance in the developing brain.
- To identify specific glial subtypes and molecular pathways involved in hypoxia adaptation.
Main Methods:
- Stimulated Raman Scattering (SRS) microscopy with deuterium-labeled probes for in vivo metabolic visualization.
- Single-nucleus RNA sequencing (snRNA-seq) to analyze transcriptional changes.
- Genetic manipulation of Notch signaling in *Drosophila*.
Main Results:
- Acute hypoxia increased de novo lipogenesis in Eaat1-positive glia.
- Chronic hypoxia induced a metabolic shift towards acetate-derived lipid synthesis in Eaat1-positive glia.
- Notch signaling activation mimicked this acetate-favored lipogenic state and counteracted hypoxia-induced metabolic suppression.
Conclusions:
- Eaat1-positive glia exhibit Notch-dependent metabolic plasticity to support brain hypoxia tolerance.
- This mechanism involves rewiring lipid metabolism, offering insights into neurological conditions like hypoxic-ischemic brain injury.
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03:14Notch Signaling Pathway
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
03:14Notch Signaling Pathway
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
01:24Regulation of Angiogenesis and Blood Supply
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
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01:23Hypoxia
Hypoxia is a medical condition characterized by an inadequate oxygen supply to body tissues. It typically manifests as a bluish discoloration of the skin and mucosae, especially in fair-skinned individuals, when hemoglobin (Hb) saturation drops below 75%.
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There are four primary types of hypoxia, each resulting from a different cause:
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Types of Hypoxia
There are four primary types of hypoxia, each resulting from a different cause:
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