RAT METANEPHRIC ORGAN-CULTURE IN TERATO-EMBRYOLOGY

The development of the permanent mammalian kidney, or metanephros, dep ends on mesenchymal-epithelial interactions, leading to branching morp hogenesis of the ureteric bud that forms the collecting ducts and to c onversion of the metanephric mesenchyme into epithelium that forms the nephrons. Rat metanephric organ culture in which these interactions a re maintained is a valuable in vitro model system for investigating no rmal and abnormal renal organogenesis. Methods were designed to evalua te either the capacity of the ureteric bud to branch or that of the me senchyme to form nephrons. Both are based on specific staining of the ureteric bud and the glomeruli with lectins. Using this approach, we h ave shown that retinoids are potent stimulating factors of nephrogenes is, acting through an increase in the branching capacity of the ureter ic bud. On the other hand, several drugs such as gentamicin and cyclos porin A were found to reduce the number of nephrons formed in vitro. W hile gentamicin affects the early branching pattern of the ureteric bu d, cyclosporin may affect the capacity of the mesenchyme to convert in to epithelium. This methodology therefore appears a potentially useful tool for toxicological studies of new drugs.