Mechanosensitive β-catenin signaling regulates lymphatic vascular development

The Wnt/beta-catenin signaling is an evolutionarily conserved pathway that plays a pivotal role in embryonic development and adult homeostasis. However, we have limited information about the involvement of Wnt/beta-catenin signaling in the lymphatic vascular system that regulates fluid homeostasis by absorbing interstitial fluid and returning it to blood circulation. In this recent publication we report that canonical Wnt/beta-catenin signaling is highly active and critical for the formation of lymphovenus valves (LVVs) and lymphatic valves (LVs). beta-catenin directly associates with the regulatory elements of the lymphedema-associated transcription factor, FOXC2 and activates its expression in an oscillatory shear stress (OSS)-dependent manner. The phenotype of beta-catenin null embryos was rescued by FOXC2 overexpression. These results suggest that Wnt/beta-catenin signaling is a mechano-transducer that links fluid force with lymphatic vascular development.