Pkd1 and Wnt5a genetically interact to control lymphatic vascular morphogenesis in mice

Abstract

Background: Lymphatic vascular development is regulated by well-characterized signaling and transcriptional pathways. These pathways regulate lymphatic endothelial cell (LEC) migration, motility, polarity, and morphogenesis. Canonical and non-canonical WNT signaling pathways are known to control LEC polarity and development of lymphatic vessels and valves. PKD1, encoding Polycystin-1, is the most commonly mutated gene in polycystic kidney disease but has also been shown to be essential in lymphatic vascular morphogenesis. The mechanism by which Pkd1 acts during lymphangiogenesis remains unclear. Results: Here we find that loss of non-canonical WNT signaling components Wnt5a and Ryk phenocopy..