title: The somite-secreted factor Maeg promotes zebrafish embryonic angiogenesis.
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.
authors: Co-innovation Center of Neuroregeneration, Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, China.
authors: Xin
authors: X
authors: Wang
authors: Co-innovation Center of Neuroregeneration, Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, China.
authors: Wei
authors: W
authors: Yuan
authors: Co-innovation Center of Neuroregeneration, Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, China.
authors: Xueqian
authors: X
authors: Wang
authors: Medical College, Nantong University, Nantong, China.
authors: Jialing
authors: J
authors: Qi
authors: Co-innovation Center of Neuroregeneration, Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, China.
authors: Yinyin
authors: Y
authors: Qin
authors: Co-innovation Center of Neuroregeneration, Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, China.
authors: Yunwei
authors: Y
authors: Shi
authors: Medical College, Nantong University, Nantong, China.
authors: Jie
authors: J
authors: Zhang
authors: School of life science, Nantong University, Nantong, China.
authors: Jie
authors: J
authors: Gong
authors: Co-innovation Center of Neuroregeneration, Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, China.
authors: Zhangji
authors: Z
authors: Dong
authors: Co-innovation Center of Neuroregeneration, Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, China.
authors: Xiaoyu
authors: X
authors: Liu
authors: Co-innovation Center of Neuroregeneration, Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, China.
authors: Chen
authors: C
authors: Sun
authors: Co-innovation Center of Neuroregeneration, Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, China.|Key Laboratory for Developmental Genes and Human Disease, Ministry of Education, Institute of Life Sciences, Southeast University, Nanjing, China.
authors: Renjie
authors: R
authors: Chai
authors: Department of Cell and Developmental Biology, Karlsruhe Institute of Technology, Karlsruhe, Germany.
authors: Ferdinand
authors: F
authors: Le Noble
authors: Co-innovation Center of Neuroregeneration, Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, China.
authors: Dong
authors: D
authors: Liu
mesh_terms: D000818:Animals; D018507:Gene Expression Regulation, Developmental; D055786:Gene Knockout Techniques; D020935:MAP Kinase Signaling System; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D011554:Pseudopodia / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism; D019170:Somites / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D008562:Membrane Glycoproteins; D051880:Receptors, Notch; D029961:Zebrafish Proteins
keywords: Maeg; Notch; angiogenesis; integrin; zebrafish