Nogo-B receptor is essential for angiogenesis in zebrafish via Akt pathway.
Our previous work has shown that axon guidance gene family Nogo-B and its receptor (NgBR) are essential for chemotaxis and morphogenesis of endothelial cells in vitro. To investigate NogoB-NgBR function in vivo, we cloned the zebrafish ortholog of both genes and studied loss of function in vivo using morpholino antisense technology. Zebrafish ortholog of Nogo-B is expressed in somite while expression of zebrafish NgBR is localized in intersomitic vessel (ISV) and axial dorsal aorta during embryonic development. NgBR or Nogo-B knockdown embryos show defects in ISV sprouting in the zebrafish trunk. Mechanistically, we found that NgBR knockdown not only abolished its ligand Nogo-B-stimulated endothelial cell migration but also reduced the vascular endothelial growth factor (VEGF)-stimulated phosphorylation of Akt and vascular endothelial growth factor-induced chemotaxis and morphogenesis of human umbilical vein endothelial cells. Further, constitutively activated Akt (myristoylated [myr]Akt) or human NgBR can rescue the NgBR knockdown umbilical vein endothelial cell migration defects in vitro or NgBR morpholino-caused ISV defects in vivo. These data place Akt at the downstream of NgBR in both Nogo-B- and VEGF-coordinated sprouting of ISVs. In summary, this study identifies the in vivo functional role for Nogo-B and its receptor (NgBR) in angiogenesis in zebrafish.
Zhao
Baofeng
B
Division of Pediatric Surgery and Division of Pediatric Pathology, Department of Surgery and Department of Pathology, Medical College of Wisconsin, Children's Research Institute, Milwaukee, WI, USA.
Chun
Changzoon
C
Liu
Zhong
Z
Horswill
Mark A
MA
Pramanik
Kallal
K
Wilkinson
George A
GA
Ramchandran
Ramani
R
Miao
Robert Q
RQ
D000818:Animals; D002633:Chemotaxis; D047108:Embryonic Development; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D018919:Neovascularization, Physiologic; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D016372:RNA, Antisense / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000502:physiology*
C541256:Nogo receptor, zebrafish; D016372:RNA, Antisense; D011956:Receptors, Cell Surface; D042461:Vascular Endothelial Growth Factor A; D029961:Zebrafish Proteins; D051057:Proto-Oncogene Proteins c-akt
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