Role of delta-like-4/Notch in the formation and wiring of the lymphatic network in zebrafish


  • I. Geudens
  • R. Herpers
  • K. Hermans
  • I. Segura
  • C. Ruiz de Almodovar
  • J. Bussmann
  • F. De Smet
  • W. Vandevelde
  • B.M. Hogan
  • A. Siekmann
  • F. Claes
  • J.C. Moore
  • A.S. Pistocchi
  • S. Loges
  • M. Mazzone
  • G. Mariggi
  • F. Bruyère
  • F. Cotelli
  • D. Kerjaschki
  • A. Noël
  • J.M. Foidart
  • H. Gerhardt
  • A. Ny
  • T. Langenberg
  • N.D. Lawson
  • H.J. Duckers
  • S. Schulte-Merker
  • P. Carmeliet
  • M. Dewerchin


  • Arteriosclerosis Thrombosis and Vascular Biology


  • Arterioscler Thromb Vasc Biol 30 (9): 1695-1702


  • Objective: To study whether Notch signaling, which regulates cell fate decisions and vessel morphogenesis, controls lymphatic development. Methods and results: In zebrafish embryos, sprouts from the axial vein have lymphangiogenic potential because they give rise to the first lymphatics. Knockdown of delta-like-4 (Dll4) or its receptors Notch-1b or Notch-6 in zebrafish impaired lymphangiogenesis. Dll4/Notch silencing reduced the number of sprouts producing the string of parchordal lymphangioblasts; instead, sprouts connecting to the intersomitic vessels were formed. At a later phase, Notch silencing impaired navigation of lymphatic intersomitic vessels along their arterial templates. Conclusion: These studies imply critical roles for Notch signaling in the formation and wiring of the lymphatic network.