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Nogo-B receptor is essential for angiogenesis in zebrafish via Akt pathway. Blood 2010 Dec 09;116(24):5423-33

Date

09/04/2010

Pubmed ID

20813898

Pubmed Central ID

PMC3012551

DOI

10.1182/blood-2010-02-271577

Abstract

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.

Author List

Zhao B, Chun C, Liu Z, Horswill MA, Pramanik K, Wilkinson GA, Ramchandran R, Miao RQ

Author

Ramani Ramchandran PhD Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Chemotaxis
Embryonic Development
Endothelial Cells
Endothelium, Vascular
Humans
Neovascularization, Physiologic
Phosphorylation
Proto-Oncogene Proteins c-akt
RNA, Antisense
Receptors, Cell Surface
Vascular Endothelial Growth Factor A
Zebrafish
Zebrafish Proteins
jenkins-FCD Prod-484 8aa07fc50b7f6d102f3dda2f4c7056ff84294d1d