The somite-secreted factor Maeg promotes zebrafish embryonic angiogenesis
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Xin Wang1,*, Wei Yuan1,*, Xueqian Wang1,*, Jialing Qi2, Yinyin Qin1, Yunwei Shi1, Jie Zhang2, Jie Gong3, Zhangji Dong1, Xiaoyu Liu1, Chen Sun1, Renjie Chai1,4, Ferdinand Le Noble5, Dong Liu1
1Co-innovation Center of Neuroregeneration, Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, China
2Medical College, Nantong University, Nantong, China
3School of life science, Nantong University, Nantong, China
4Key Laboratory for Developmental Genes and Human Disease, Ministry of Education, Institute of Life Sciences, Southeast University, Nanjing, China
5Department of Cell and Developmental Biology, Karlsruhe Institute of Technology, Karlsruhe, Germany
*These authors have contributed equally to this work
Keywords: Maeg, angiogenesis, integrin, Notch, zebrafish
Received: May 09, 2016 Accepted: October 12, 2016 Published: October 21, 2016
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.
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