Combining Foxc2 and Connexin37 deletions in mice leads to severe defects in lymphatic vascular growth and remodeling.

摘要: Abstract Connexins (Cxs), proteins that are vital for intercellular communication in vertebrates, have recently been shown to play a critical role lymphatic development. However, our knowledge is currently limited regarding the functional relationships of Cxs with other and signaling pathways. Cell culture studies Cx37 necessary coordinated activation transcription factor NFATc1, which cooperates Foxc2 (another factor) during endothelial These data suggest Cxs, Foxc2, NFATc1 part common developmental pathway. Here, we present detailed characterization Foxc2+/−Cx37−/− mice, demonstrating network architecture valve formation rely on concurrent embryonic expression function Cx37. mice lymphedema utero, exhibit craniofacial abnormalities, show severe dilation intestinal lymphatics, display abnormal lacteal development, lack valves, typically die perinatally (outcomes not seen Foxc2+/− or Cx37−/− separately). We provide rigorous, quantitative documentation vascular changes highlight specific structural alterations occur mice. further evidence suggesting elements molecular pathway directing lymphangiogenesis.