The somite-secreted factor Maeg promotes zebrafish embryonic angiogenesis

// Xin Wang 1, * , Wei Yuan 1, * , Xueqian Wang 1, * , Jialing Qi 2 , Yinyin Qin 1 , Yunwei Shi 1 , Jie Zhang 2 , Jie Gong 3 , Zhangji Dong 1 , Xiaoyu Liu 1 , Chen Sun 1 , Renjie Chai 1, 4 , Ferdinand Le Noble 5 , Dong Liu 1 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 * These authors have contributed equally to this work Correspondence to: Dong Liu, email: liudongtom@gmail.com , tom@ntu.edu.cn Keywords: Maeg, angiogenesis, integrin, Notch, zebrafish Received: May 09, 2016     Accepted: October 12, 2016     Published: October 21, 2016 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.