The lymphatic vasculature is a crucial component of the cardiovascular system, with vital roles in tissue homeostasis, immune cell trafficking and absorption of lipids from the digestive system. Although signalling events important for the development of the blood vasculature system have been thoroughly investigated, less is known about the signalling pathways involved in development of the lymphatic vasculature. Our work has revealed that the ubiquitin ligase Nedd4 is crucial for morphogenesis of the lymphatic vasculature during mouse embryogenesis; Nedd4-/- embryos exhibiting strikingly mis-patterned dermal lymphatic vessels. Furthermore, conditional deletion of Nedd4 from lymphatic endothelial cells using the Prox1CreERT2 mouse line results in aberrant dermal lymphatic vessel patterning, demonstrating a cell autonomous role for Nedd4 in lymphatic development. Ubiquitination regulates the function of an array of proteins by controlling their stability, subcellular localisation or degradation. Here, we provide evidence demonstrating that Nedd4 regulates lymphatic vascular development in a cell autonomous manner by controlling the abundance and trafficking of VEGF receptors, leading to reduced signalling in response to VEGF-C. Furthermore, we demonstrate that Nedd4 regulates the remodelling of lymphatic endothelial cell adherens junctions; in the absence of Nedd4, the failure of junctional remodelling results in decreased capacity of lymphatic endothelial cells to migrate in response to VEGF-C. Current work aims to identify the substrates of Nedd4 responsible for regulating lymphangiogenesis.