Temporally compartmentalized expression of ephrin-B2 during renal glomerular development

Glomerular development proceeds through the spatially ordered and sequentia l recruitment, proliferation, assembly, and differentiation of endothelial, mesangial, and epithelial. progenitors. The molecular determinants of cell -cell recognition and targeting in this process have yet to be defined. The Eph/ephrin family of membrane receptors and counterreceptors are critical participants of developmental vascular assembly in extrarenal sites. Renal expression patterns of ephrin-132 and EphB4 were investigated using mice ex pressing beta -galactosidase under control of ephrin-132 or EphB4 promoters . The earliest glomerular expression of ephrin-132 was identified in a subs et of differentiating comma-stage glomerular epithelial cells (podocyte pro genitors) adjacent to the vascular cleft where endothelial progenitors are subsequently recruited. Epithelial ephrin-132 expression was accompanied by expression in endothelial and mesangial cells as capillary assembly progre ssed. At or near completion of glomerular maturation, epithelial ephrin-132 expression was extinguished, with persistence in glomerular endothelial ce lls. Throughout development, one of several ephrin-132 receptors, EphB4, wa s persistently and exclusively expressed in endothelial cells of venous str uctures. The findings show sequential ephrin-B2 expression across glomerula r lineages, first in a distinct subset of podocyte progenitors and subseque ntly in endothelial cells of the developing glomerulus. Given targeting fun ctions for Eph/ephrin family proteins, the findings suggest that ephrin-132 expression marks podocyte progenitors at the site of vascular cleft format ion, where expression may establish an "address" to which endothelial and m esangial progenitors axe recruited. Thus, the present results suggest that ephrin-B2 and EphB; interactions play an important role in glomerular micro vascular assembly.