Role of Dll4/Notch in the Formation and Wiring of the Lymphatic Network in Zebra Fish

OBJECTIVE: To study whether Notch signaling, which regulates cell fate decisions and vessel morphogenesis, controls lymphatic development. METHODS AND RESULTS: In zebra fish embryos, sprouts from the axial vein have lymphangiogenic potential because they produce the first lymphatics. Knockdown of Dll4 or its receptors (Notch-1b or Notch-6) in zebra fish 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. CONCLUSIONS: These studies imply critical roles for Notch signaling in the formation and wiring of the lymphatic network.