EARLY DEFECT IN BRANCHING MORPHOGENESIS OF THE URETERAL BUD IN INDUCED NEPHRON DEFICIT

Development of the metanephric kidney during embryogenesis can be alte red both in vivo and in vitro by exposure to gentamicin, which may lea d to oligonephronia. To study the role of the ureteric bud in nephron deficit genesis, we used metanephros organ cultures exposed to gentami cin as a model of impaired nephrogenesis. Ultrastructural localization of the antibiotic showed that by eight hours it was already present w ithin the epithelial cells of the ureteric bud and in its growing ends , and also trapped in the adjacent blastema. Using confocal microscopy and image analysis, we devised a quantitative approach to analyze the branching pattern of the ureteric bud, and showed that by 24 hours of culture, despite no change of explants growth, gentamicin had signifi cantly decreased the number of branching points. This effect involved the early branching events and was limited to end buds that had no nep hron anlagen nearby. Our findings indicate that impaired branching mor phogenesis of the ureteric bud is the likely event of gentamicin-induc ed nephron deficit.