Role of Delta-like-4/Notch in the Formation and Wiring of the Lymphatic Network in Zebrafish

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. (Arterioscler Thromb Vasc Biol. 2010; 30: 1695-1702.)