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Oncotarget. 2016 Nov 22;7(47):77749-77763. doi: 10.18632/oncotarget.12793.

The somite-secreted factor Maeg promotes zebrafish embryonic angiogenesis.

Author information

1
Co-innovation Center of Neuroregeneration, Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, China.
2
Medical College, Nantong University, Nantong, China.
3
School of life science, Nantong University, Nantong, China.
4
Key Laboratory for Developmental Genes and Human Disease, Ministry of Education, Institute of Life Sciences, Southeast University, Nanjing, China.
5
Department of Cell and Developmental Biology, Karlsruhe Institute of Technology, Karlsruhe, Germany.

Abstract

MAM and EGF containing gene (MAEG), also called Epidermal Growth Factor-like domain multiple 6 (EGFL6), belongs to the epidermal growth factor repeat superfamily. The role of Maeg in zebrafish angiogenesis remains unclear. It was demonstrated that maeg was dynamically expressed in zebrafish developing somite during a time window encompassing many key steps in embryonic angiogenesis. Maeg loss-of-function embryos showed reduced endothelial cell number and filopodia extensions of intersegmental vessels (ISVs). Maeg gain-of-function induced ectopic sprouting evolving into a hyperbranched and functional perfused vasculature. Mechanistically we demonstrate that Maeg promotes angiogenesis dependent on RGD domain and stimulates activation of Akt and Erk signaling in vivo. Loss of Maeg or Itgb1, augmented expression of Notch receptors, and inhibiting Notch signaling or Dll4 partially rescued angiogenic phenotypes suggesting that Notch acts downstream of Itgb1. We conclude that Maeg acts as a positive regulator of angiogenic cell behavior and formation of functional vessels.

KEYWORDS:

Maeg; Notch; angiogenesis; integrin; zebrafish

PMID:
27780917
PMCID:
PMC5363618
DOI:
10.18632/oncotarget.12793
[Indexed for MEDLINE]
Free PMC Article

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