The vertebrate lymphatic vasculature is essential for normal tissue fluid drainage and immune cell trafficking. Insufficient lymphatic development can lead to lymphoedema, while on the flip side excessive lymphangiogenesis contributes to the spread of cancer and is central in the aetilogy of a number of vascular pathologies. To understand fundamental molecular mechanisms common in development and disease we have used complementary large scale forward genetic screens and targeted reverse genetic screening approaches. Recently, we have uncovered unexpected roles for pre-mRNA splicing and its regulation by Nova2 in both zebrafish and mouse. We have also characterised unexpected new targets of the Hippo signalling pathway and its transcriptional effector Yap1 that are essential to drive lymphangiogenesis. In this talk, we will explore these new and unexpected mechanisms of lymphangiogenesis as well as sharing several early unpublished observations.