Deciphering the cellular origin of dermal lymphatics during embryonic development

C Pichol-Thievend1, K Betterman2, R Skoczylas1, E Lesieur1, BM Hogan1, NL Harvey2 and M Francois1

  1. Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Queensland, Australia
  2. Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, South Australia, Australia

Despite essential role of the lymphatic vascular system in the regulation of tissue homeostasis and in diseases, the cellular basis of its embryonic development is still poorly understood. The actual model is that a discrete population of endothelial cells in embryonic veins constitutes the sole origin of the entire lymphatic vasculature. However recent findings have challenged this dogma proposing the hemogenic endothelium as a second source of lymphatic endothelial cell (LEC) during organ-specific lymphangiogenesis. By using lineage-tracing approach and assessing endogenous gene expression of lymphatic markers, we discovered the induction of Prox1 expression in endothelial cell from a primary blood vascular plexus in the skin. Taking advantage of high-resolution imaging techniques, we show the extrusion of differentiating LECs cluster from local blood vessels. To investigate the contribution of the hemogenic endothelium in LEC cluster formation during skin development, we used conditional Gata2 loss of function. Genetic disruption of Gata2 did not impair the emergence of these new LEC progenitors. This study provides a novel insight in the cellular mechanisms that drive the formation of the lymphatic vasculature during skin organogenesis. Our finding raises the question whether a similar mechanism would be at play during pathological lymphangiogenesis.