Differentiation of arterial and venous endothelial cells and vascular morphogenesis

Masanori Hirashima, Toshio Suda

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)


The vascular system is comprised of an organized hierarchical structure of arteries, veins, and capillaries. Recent studies in zebrafish, chick, and mouse reveal that the identity of artery and vein is governed by genetic factors as well as blood flow. The ephrin/Eph system establishes arterial and venous endothelial cell identity, and is important for structural segregation between arteries and veins. Analyses using loss- or gain-of-function mutations in zebrafish and mice show that Su(H)/ RBP-J-dependent Delta/Notch signaling is a key mediator of arterial endothelial cell fate decision and vascular patterning. Vascular endothelial growth factor has also been shown to work upstream of Notch and is a key player in arteriogenesis. On the other hand, an orphan nuclear receptor, COUP-TFII, induces venous endothelial cell differentiation by suppressing the Notch signaling. Arteriovenous malformations are frequently induced by a loss of arterial and venous cell specification. These insights indicate that the balance of these genetic factors and modification by epigenetic factors such as hemodynamics and oxygen tension are important for proper endothelial cell identities in vascular morphogenesis.

Original languageEnglish
Pages (from-to)137-145
Number of pages9
JournalEndothelium: Journal of Endothelial Cell Research
Issue number2
Publication statusPublished - 2006 Mar
Externally publishedYes


  • Artery
  • Endothelial cells
  • Mouse
  • Notch
  • VEGF
  • Vascular morphogenesis
  • Vein
  • Zebrafish

ASJC Scopus subject areas

  • Physiology
  • Cell Biology


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