Lymphangiogenesis, the formation of lymphatic vessels, involves multiple growth factors and receptors, including vascular endothelial growth factor C (VEGFC) and its receptor VEGFR3. Here, on , Yoh-suke Mukouyama and co-workers uncover a role for TGFβ signalling during lymphatic network development in mice. The researchers first develop a novel, whole-mount imaging technique to visualise lymphatic vessels in the anterior dorsal skin of mouse embryos. Using this approach, combined with conditional knockout of TGFβ receptors (Tgfbr1 or Tgfbr2) in lymphatic endothelial cells (LECs), they show that a loss of TGFβ signalling in LECs leads to reduced vessel sprouting and hence a global decrease in lymphatic network complexity. Furthermore, they report, LEC proliferation is increased following TGFβ receptor depletion. Finally, they demonstrate that TGFβ signalling in a dermal lymphatic cell line can upregulate the expression of VEGFR3 and the VEGFC co-receptor neuropilin 2. These studies, together with other findings, suggest that TGFβ plays a dual role during lymphangiogenesis, both enhancing LEC sprouting while decreasing LEC proliferation.
