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.

gene silencing, lymphangiogenesis, notch signaling, vascular biology, zebrafish
dx.doi.org/10.1161/ATVBAHA.110.203034, hdl.handle.net/1765/20853
Arteriosclerosis, Thrombosis, and Vascular Biology
Erasmus MC: University Medical Center Rotterdam

Geudens, I, Herpers, R.L.J.M, Hermans, K, Segura, I, Ruiz De Almodovar, C, Bussmann, J, … Dewerchin, M. (2010). Role of delta-like-4/notch in the formation and wiring of the lymphatic network in zebrafish. Arteriosclerosis, Thrombosis, and Vascular Biology, 30(9), 1695–1702. doi:10.1161/ATVBAHA.110.203034