Vegfa signaling regulates diverse artery/vein formation in vertebrate vasculatures

Daqing Jin^{a, c, #},
Diqi Zhu^{b, #},
Yabo Fang^a,
Yiwei Chen^b,
Gaihong Yu^{a, c},
Weijun Pan^d,
Dong Liu^e,
Fen Li^{b
, ,},
Tao P. Zhong^{a, c
, ,}

a.
State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhong Shan Hospital, Fudan University, Shanghai 200438, China
b.
Department of Pediatric Cardiology, Shanghai Children's Medical Center Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200127, China
c.
Shanghai Key Laboratory of Regulatory Biology, Institute of Molecular Medicine, School of Life Sciences, East China Normal University, Shanghai 200241, China
d.
Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China
e.
Co-innovation Center of Neuroregeneration, Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong 226001, China

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Corresponding author: E-mail address: lifen@scmc.com.cn (Fen Li); E-mail address: tzhong@bio.ecnu.edu.cn (Tao P. Zhong)

These authors contributed equally to this work.

摘要

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Abstract: Vascular endothelial growth factor A (Vegfa) signaling regulates vascular development during embryogenesis and organ formation. However, the signaling mechanisms that govern the formation of various arteries/veins in various tissues are incompletely understood. In this study, we utilized transcription activator-like effector nuclease (TALEN) to generate zebrafish vegfaa mutants. vegfaa embryos are embryonic lethal, and display a complete loss of the dorsal aorta (DA) and expansion of the cardinal vein. Activation of Vegfa signaling expands the arterial cell population at the expense of venous cells during vasculogenesis of the axial vessels in the trunk. Vegfa signaling regulates endothelial cell (EC) proliferation after arterial-venous specification. Vegfa deficiency and overexpression inhibit the formation of tip cell filopodia and interfere with the pathfinding of intersegmental vessels (ISVs). In the head vasculature,vegfaa^‒/‒ causes loss of a pair of mesencephalic veins (MsVs) and central arteries (CtAs), both of which usually develop via sprouting angiogenesis. Our results indicate that Vegfa signaling induces the formation of the DA at the expense of the cardinal vein during the trunk vasculogenesis, and that Vegfa is required for the angiogenic formation of MsVs and CtAs in the brain. These findings suggest that Vegfa signaling governs the formation of diverse arteries/veins by distinct cellular mechanisms in vertebrate vasculatures.
- Vegfa /
- TALEN /
- Arterial-venous specification /
- Zebrafish
These authors contributed equally to this work.
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doi: 10.1016/j.jgg.2017.07.005

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Vegfa signaling regulates diverse artery/vein formation in vertebrate vasculatures

Corresponding author: E-mail address: lifen@scmc.com.cn (Fen Li); E-mail address: tzhong@bio.ecnu.edu.cn (Tao P. Zhong)

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doi: 10.1016/j.jgg.2017.07.005

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Vegfa signaling regulates diverse artery/vein formation in vertebrate vasculatures

Corresponding author: E-mail address: lifen@scmc.com.cn (Fen Li); E-mail address: tzhong@bio.ecnu.edu.cn (Tao P. Zhong)

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