Development of the avian lymphatic system

Recently, highly specific markers of the lymphatic endothelium have been fo und enabling us to reinvestigate the embryonic origin of the lymphatics. He re we present a review of our studies on the development of the lymphatic s ystem in chick and quail embryos. We show that the lymphatic endothelium is derived from two sources: the embryonic lymph sacs and mesenchymal lymphan gioblasts. Proliferation studies reveal a BrdU-labeling index of 11.5% of l ymph sac endothelial cells by day 6.25, which drops to 3.5% by day 7. Lymph angioblasts are able to integrate into the lining of lymph sacs. Lymphatic endothelial cells express the vascular endothelial growth factor (VEGF) rec eptors-2 and -3. Their ligand, VEGF-C, is expressed almost ubiquitously in embryonic and fetal tissues. Elevated expression levels are found in the tu nica media of large blood vessels, which usually serve as major routes for growing lymphatics. The homeobox gene, Prox1, is expressed in lymphatic but not in blood vascular endothelial cells throughout all stages examined, na mely, in developing lymph sacs of day 6 embryos and in lymphatics at day 16 . Experimental studies show the existence of lymphangioblasts in the mesode rm, a considerable time before the development of the lymph sacs. Lymphangi oblasts migrate from the somites into the somatopleure and contribute to th e lymphatics of the limbs. Our studies indicate that these lymphangioblasts already express Prox1. (C) 2001 Wiley-Liss, Inc.