Notch Leads Lymphatics and Links Them to Blood Vessels

Abstract

Lymphatic vessels sprout from the cardinal vein to form primary lymphatic sacs.1,2 However, molecular mechanisms that guide the formation of a mature functional lymphatic network are still shrouded in mystery. Several molecules that are considered markers of arterial endothelial cells (ECs), such as ephrin B2, Foxc2, and integrin α9, are involved in lymphangiogenesis.1 By using an elegant in vivo approach, Geudens et al3 added another arterial factor to this constellation of molecules. Specifically, they show that Notch (a regulator of cell fate decisions and blood vessel development) is also required for lymphatic network development. By systematically silencing zebra fish orthologues of the Notch family receptors (Notch 1a/b, Notch 5, and Notch 6) and their ligands (jagged 1a/b, jagged-2, delta A-D, and deltalike [Dll] 4) and then tracing blood and lymphatic ECs (LECs) during zebra fish embryogenesis, they reveal the critical role of Notch signaling in the guidance of lymphatics and the formation of a lymphatic network. See accompanying article on page 1695 Notch is known to control endothelial sprouting during angiogenesis.4 During embryogenesis, lymphangiogenesis occurs after angiogenesis, making it difficult to dissect whether and how Notch regulates lymphatic development in mouse models. To this end, Geudens et al3 took advantage of zebra fish as a model organism to study angiogenesis and lymphangiogenesis and …