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Blood vessels regulate primary motor neuronal pathfinding in zebrafish via exosome contained microRNA-22

Jiajing Sheng, Jie Gong, Yunwei Shi, Xin Wang, View ORCID ProfileDong Liu
doi: https://doi.org/10.1101/2021.04.29.441918
Jiajing Sheng
1School of Life Science, Nantong Laboratory of Development and Diseases; Second Affiliated Hospital; Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China
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Jie Gong
1School of Life Science, Nantong Laboratory of Development and Diseases; Second Affiliated Hospital; Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China
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Yunwei Shi
1School of Life Science, Nantong Laboratory of Development and Diseases; Second Affiliated Hospital; Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China
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Xin Wang
1School of Life Science, Nantong Laboratory of Development and Diseases; Second Affiliated Hospital; Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China
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Dong Liu
1School of Life Science, Nantong Laboratory of Development and Diseases; Second Affiliated Hospital; Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China
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  • ORCID record for Dong Liu
  • For correspondence: liudongtom@gmail.com tom@ntu.edu.cn
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Abstract

A precise neuro-vascular communication is crucial to orchestrate directional migration and patterning of the complex vascular network and neural system. However, how blood vessels are involved in shaping the proper neuronal formation has not been fully understood. 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 ECs resulted in the patterning defects of both ISVs and PMNs. However, neuronal block of miR-22a mainly led to the axonal defects of PMN. Then we demonstrated that endothelial miR-22a regulates PMNs axonal navigation via exosome pathway. Sema4c was identified as a potential target of miR-22a through transcriptomic analysis and in silico analysis. Furthermore, luciferase assay and EGFP sensor assay in vivo confirmed the binding of miR-22a with 3’-UTR of sema4c. In addition, Down-regulation of sema4c in the miR-22a morphants significantly neutralized the aberrant patterning of vascular and neural networks. Our study revealed that miR-22a acted as a dual guidance cue coordinating vascular and neuronal patterning and expanded the repertoire of guidance molecules, which might be of use therapeutically to guide vessels and nerves in the relevant diseases that affect both systems.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted April 29, 2021.
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Blood vessels regulate primary motor neuronal pathfinding in zebrafish via exosome contained microRNA-22
Jiajing Sheng, Jie Gong, Yunwei Shi, Xin Wang, Dong Liu
bioRxiv 2021.04.29.441918; doi: https://doi.org/10.1101/2021.04.29.441918
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Blood vessels regulate primary motor neuronal pathfinding in zebrafish via exosome contained microRNA-22
Jiajing Sheng, Jie Gong, Yunwei Shi, Xin Wang, Dong Liu
bioRxiv 2021.04.29.441918; doi: https://doi.org/10.1101/2021.04.29.441918

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