論文 - 詳細
| RRC ID | 87483 |
|---|---|
| 著者 | Bassi I, Grunspan M, Hen G, Ravichandran KA, Moshe N, Gutierrez-Miranda L, Safriel SR, Kostina D, Shen A, Ruiz de Almodovar C, Yaniv K. |
| タイトル | Endolysosomal dysfunction in radial glia progenitor cells leads to defective cerebral angiogenesis and compromised blood-brain barrier integrity. |
| ジャーナル | Nat Commun |
| Abstract |
The neurovascular unit (NVU) is a complex multicellular structure that helps maintain cerebral homeostasis and blood-brain barrier (BBB) integrity. While extensive evidence links NVU alterations to cerebrovascular diseases and neurodegeneration, the underlying molecular mechanisms remain unclear. Here, we use zebrafish embryos carrying a mutation in Scavenger Receptor B2, a highly conserved endolysosomal protein expressed predominantly in Radial Glia Cells (RGCs), to investigate the interplay among different NVU components. Through live imaging and genetic manipulations, we demonstrate that compromised acidification of the endolysosomal compartment in mutant RGCs leads to impaired Notch3 signaling, thereby inducing excessive neurogenesis and reduced glial differentiation. We further demonstrate that alterations to the neuron/glia balance result in impaired VEGF and Wnt signaling, leading to severe vascular defects, hemorrhages, and a leaky BBB. Altogether, our findings provide insights into NVU formation and function and offer avenues for investigating diseases involving white matter defects and vascular abnormalities. |
| 巻・号 | 15(1) |
| ページ | 8158 |
| 公開日 | 2024-9-17 |
| DOI | 10.1038/s41467-024-52365-8 |
| PII | 10.1038/s41467-024-52365-8 |
| PMID | 39289367 |
| PMC | PMC11408700 |
| MeSH | Angiogenesis Animals Animals, Genetically Modified Blood-Brain Barrier* / metabolism Blood-Brain Barrier* / pathology Brain / blood supply Brain / metabolism Brain / pathology Cell Differentiation Endosomes / metabolism Ependymoglial Cells / metabolism Ependymoglial Cells / pathology Lysosomes* / metabolism Mutation Neovascularization, Physiologic Neurogenesis* Neuroglia / metabolism Neuroglia / pathology Receptors, Notch / genetics Receptors, Notch / metabolism Signal Transduction Stem Cells / metabolism Vascular Endothelial Growth Factor A / genetics Vascular Endothelial Growth Factor A / metabolism Wnt Signaling Pathway Zebrafish* Zebrafish Proteins* / genetics Zebrafish Proteins* / metabolism |
| IF | 12.121 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 56 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ゼブラフィッシュ | Tg(gfap:dTomato) Tg(gfap:Gal4FF)wa32 Tg(CM-isl1:GFP)rw0 |