Dr. Yang, Ruey-Bing (Ray)'s publons link picture

Dr. Yang, Ruey-Bing (Ray)

Acting Director
Research Fellow
  • (02) 2789-9063 (Lab) (Room No: N427)
  • (02) 2652-3943
  • (02) 2785-8847 (Fax)


Signal transduction

Receptor biology

Vascular biology

Education and Positions:
  • Ph.D., University of Texas Southwestern Medical Center at Dallas

    Postdoctoral Fellow, Genentech, Inc.

Highlight Detail

Zebrafish scube1 and scube2 cooperate in promoting Vegfa signaling during embryonic vascularization

Dr. Yang, Ruey-Bing (Ray)
Cardiovascular Research, Mar 31, 2021

The secreted and membrane-anchored signal peptide-CUB-EGF domain-containing proteins (SCUBE) gene family composed of three members was originally identified from endothelial cells (ECs). We recently showed that membrane SCUBE2 binds vascular endothelial growth factor (VEGF) and acts as a co-receptor for VEGF receptor 2 to modulate EC migration, proliferation, and tube formation during postnatal and tumour angiogenesis. However, whether these SCUBE genes cooperate in modulating VEGF signalling during embryonic vascular development remains unknown.

Methods and results

To further dissect the genetic interactions of these scube genes, transcription activator-like effector nuclease-mediated genome editing was used to generate knockout (KO) alleles of each scube gene. No overt vascular phenotypes were seen in any single scube KO mutants because of compensation by other scube genes during zebrafish development. However, scube1 and scube2 double KO (DKO) severely impaired EC filopodia extensions, migration, and proliferation, thus disrupting proper vascular lumen formation during vasculogenesis and angiogenesis as well as development of the organ-specific intestinal vasculature. Further genetic, biochemical, and molecular analyses revealed that Scube1 and Scube2 might act cooperatively at the cell-surface receptor level to facilitate Vegfa signalling during zebrafish embryonic vascularization.


We showed for the first time that cooperation between scube1 and scube2 is critical for proper regulation of angiogenic cell behaviours and formation of functional vessels during zebrafish embryonic development.