Expression of lymphatic endothelium-specific hyaluronan receptor LYVE-1 in the developing mouse kidney

Our knowledge of the embryonic development of the lymphatic vessels within the kidney is limited. The aim of this study was to establish the time of appearance and the distribution of intra-renal lymphatic vessels in the developing mouse kidney by using the lymphatic marker, LYVE-1. Kidneys from embryonic day 12 (E12) to E18, from neonates at post-natal day 1 (P1) to P21, and from adults were studied. In the adult mouse kidney, LYVE-1 was expressed mainly in the lymphatic endothelial cells (LECs) and in a subset of endothelial cells in the glomerular capillaries. However, in the developing mouse kidney, LYVE-1 was also expressed transiently in F4/80⁺/CD11b^- immature macrophages/dendritic cells and in the developing renal vein. LYVE-1⁺ lymphatic vessels connected with extra-renal lymphatics were detected in the kidney at E13. F4/80⁺/CD11b^-/LYVE-1 ⁺ immature macrophages/dendritic cells appeared prior to the appearance of LYVE-1⁺ renal lymphatic vessels and were closely intermingled or even formed part of the lymphatic vascular wall. Prox1 was expressed only in the LYVE-1⁺ LECs from fetus to adulthood, but not in LYVE-1⁺ endothelial cells of the developing renal vein and macrophages/dendritic cells. Thus, lymphatic vessels of the kidney might originate by extension of extra-renal lymphatics through an active branching process possibly associated with F4/80⁺/ CD11b^-/LYVE- 1⁺ macrophages/dendritic cells.