ELK AND LERK-2 IN DEVELOPING KIDNEY AND MICROVASCULAR ENDOTHELIAL ASSEMBLY

Eph family receptor tyrosine kinases direct neuronal cell targeting, b undling and intercellular aggregation activity, yet their role in mamm alian kidney development has been unexplored to date. We recently iden tified expression of ELK (Eph-like kinase) receptors in cultured human renal microvascular endothelial cells (HRMEC), and showed that ELK me diates their in vitro assembly into capillary-like structures in respo nse to the exogenous ligand, LERK-2. Here we identify expression of th e ELK ligand, LERK-2, in HRMEC and in primitive vascular structures of developing murine kidney. ELK and LERK-2 are expressed on endothelial progenitor cells of primitive microvasculature in a pattern similar t o that of the VEGF receptor, flk-1. ELK, LERK-2 and flk-1 antigens are also displayed on the branching ureteric bud epithelium; ELK and LERK -2 expression persists in mature collecting ducts, glomeruli and arter ioles. To explore whether renal-derived endothelial cells may distingu ish LERK-2 from the angiogenic Eck ligand, LERK-1 (B61), and whether e ndothelial cells from different sources may distinguish among Eph rece ptor ligands, we compared HRMEC and human umbilical vein endothelial c ell (HUVEC) responses in an in vitro capillary-like assembly assay. HR MEC endothelial cells assembled capillary-like structures in response to LERK-2, but not LERK-1, under conditions that promoted HUVEC to ass emble in response to LERK-1, but not LERK-2. Therefore, responses medi ated through specific Eph family receptors (ELK and Eck) are discrimin ated by endothelial cells from different vascular bed sources. ELK and its ligand, LERK-2, are spatially and temporally coordinated in expre ssion and may function in morphogenesis of the renal microvasculature.