PUBLICATION

Regulation of Hindbrain Vascular Development by rps20 in Zebrafish

Authors
Shen, X., Wen, Z., Deng, S., Qiu, Y., Ma, W., Dong, X., Gong, J., Zhang, Y., Liu, D., Xu, B.
ID
ZDB-PUB-250728-1
Date
2025
Source
Cells   14: (Journal)
Registered Authors
Gong, Jie, Liu, Dong
Keywords
aging, brain vasculature, rps20, vascular permeability, zebrafish
MeSH Terms
  • Endothelial Cells/metabolism
  • Animals
  • Gene Expression Regulation, Developmental
  • Ribosomal Proteins*/genetics
  • Ribosomal Proteins*/metabolism
  • Humans
  • Zebrafish*/embryology
  • Zebrafish*/genetics
  • Zebrafish*/metabolism
  • Aging/genetics
  • Zebrafish Proteins*/genetics
  • Zebrafish Proteins*/metabolism
  • Rhombencephalon*/blood supply
  • Rhombencephalon*/embryology
  • Rhombencephalon*/metabolism
  • Neovascularization, Physiologic*
PubMed
40710323 Full text @ Cells
Abstract
During aging, the brain vasculature undergoes significant deterioration characterized by increased arterial tortuosity, compromised blood-brain barrier integrity, and reduced cerebral blood flow, all of which contribute to various neurological disorders. Thus, understanding the mechanisms underlying aging-related cerebrovascular defects is critical for developing strategies to alleviate aging-associated neurological diseases. In this study, we investigated the role of aging-related genes in brain vascular development using zebrafish as an in vivo model. By thoroughly analyzing scRNA-seq datasets of mid- and old-aged brain vascular endothelial cells (human/mouse), we found ribosomal protein S20 (rps20) significantly down-regulated during aging. qPCR analysis and whole-mount in situ hybridization validated a high expression of rps20 during early zebrafish development, which progressively decreased in adult and aged zebrafish brains. Functional studies using the CRISPR/Cas9-mediated knockout of rps20 revealed an impaired growth of central arteries in the hindbrain and a marked increased intracranial hemorrhage incidence. Mechanistically, qPCR analysis demonstrated a significant downregulation of vegfa, cxcl12b, and cxcr4a, key signaling molecules required for hindbrain vascular development, in rps20-deficient embryos. In conclusion, our findings demonstrate that rps20 is essential for proper brain vascular development and the maintenance of vascular homeostasis in zebrafish, revealing a novel mechanism by which aging-related genes regulate brain vascular development. This study provides new insights that may aid in understanding and treating aging-associated vascular malformations and neurological pathologies.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping