Oral Presentation 6th Australian Health and Medical Research Congress 2012

Defining the role of the Nedd4 ubiquitin ligase during lymphatic vascular morphogenesis in the mouse embryo (#36)

Genevieve A Secker 1 , Jan S Kazenwadel 1 , Kelly L Betterman 1 , Natasha Boase 1 , Sharad Kumar 1 2 , Natasha L Harvey 1 2
  1. SA Pathology, Adelaide, SA, Australia
  2. School of Medicine, University of Adelaide, Adelaide, SA, Australia

Lymphatic vessels are vital for tissue fluid homeostasis, the absorption of dietary fats and immune cell trafficking. Despite the integral role that lymphatic vessels play in homeostasis and human disease, little is known about the signals that direct construction of the lymphatic vasculature during development. Our work is focused on the identification and characterisation of genes and signalling pathways involved in morphogenesis of the lymphatic vasculature in mice. Here, we present recent work dissecting the role of the ubiquitin ligase Nedd4 in embryonic vascular development. Protein ubiquitination is a highly conserved process that can lead to the degradation, stabilisation or change in subcellular localisation of target proteins. Our work has revealed that Nedd4 is crucial for morphogenesis of the blood and lymphatic vascular networks during mouse embryogenesis. Nedd4-/- embryos exhibit sparse, ruptured blood vessels and strikingly mispatterned lymphatic vessels. Current work aims to dissect the endothelial cell autonomous versus non-autonomous roles of Nedd4 during vascular development and to identify the protein targets of Nedd4 important for morphogenesis of the lymphatic vasculature in the mouse embryo.