PUBLICATION

MicroRNA-22 coordinates vascular and motor neuronal pathfinding via sema4 during zebrafish development

Authors
Sheng, J., Gong, J., Shi, Y., Wang, X., Liu, D.
ID
ZDB-PUB-220407-3
Date
2022
Source
Open Biology   12: 210315 (Journal)
Registered Authors
Gong, Jie, Liu, Dong, Shi, Yunwei, Wang, Xin
Keywords
endothelial cells, guidance cues, microRNA, motor neuron, pathfinding
MeSH Terms
  • Animals
  • Axon Guidance
  • Endothelial Cells/metabolism
  • MicroRNAs*/genetics
  • MicroRNAs*/metabolism
  • Zebrafish*/genetics
  • Zebrafish*/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed
35382569 Full text @ Open Biol.
Abstract
A precise guiding signal is crucial to orchestrate directional migration and patterning of the complex vascular network and neural system. So far, limited studies have reported the discovery and functions of microRNAs (miRNAs) in guiding vascular and neural pathfinding. Currently, we showed that the deficiency of miRNA-22a, an endothelial-enriched miRNA, caused dramatic pathfinding defects both in intersegmental vessels (ISVs) and primary motor neurons (PMNs) in zebrafish embryos. Furthermore, we found the specific inhibition of miR-22a in endothelial cells (ECs) resulted in patterning defects of both ISVs and PMNs. Neuronal block of miR-22a mainly led to axonal defects of PMN. Sema4c was identified as a potential target of miR-22a through transcriptomic analysis and in silico analysis. Additionally, a luciferase assay and EGFP sensor assay confirmed the binding of miR-22a with 3'-UTR of sema4c. In addition, downregulation of sema4c in the miR-22a morphants significantly neutralized the aberrant patterning of vascular and neural networks. Then we demonstrated that endothelial miR-22a regulates PMNs axonal navigation. Our study revealed that miR-22a acted as a dual regulatory cue coordinating vascular and neuronal patterning, and expanded the repertoire of regulatory molecules, which might be of use therapeutically to guide vessels and nerves in the relevant diseases.
Genes / Markers
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Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes