Zebrafish Scube1 and Scube2 cooperate in promoting Vegfa signalling during embryonic vascularization

Ku Chi Tsao, Yuh Charn Lin, Yi Ting Chen, Shih Lei Lai, Ruey Bing Yang

研究成果: 雜誌貢獻文章同行評審

1 引文 斯高帕斯(Scopus)

摘要

Aims: 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. Conclusions: 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.
原文英語
頁(從 - 到)1074-1087
頁數14
期刊Cardiovascular Research
118
發行號4
DOIs
出版狀態已發佈 - 3月 1 2022

ASJC Scopus subject areas

  • 生理學
  • 心臟病學與心血管醫學
  • 生理學(醫學)

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