TOWARDS A GENETIC-BASIS FOR KIDNEY DEVELOPMENT

Although it is not easy to investigate the regulatory basis of developmental processes in most mammalian tissues, the mouse kidney has several distinct advantages as a model System. Its development involves a wide variety of developmental processes that include induction, stem-cell regulation, a mesenchyme-to-epithelium transition, epithelial morphogenesis and pattern formation. Further, there are several genetic disorders associated with its development, much of nephrogenesis will take place in vitro and a significant start has been made in elucidating the regulatory molecules involved in its ontogeny. Here, we summarise current knowledge on how the various aspects of kidney development are controlled at the genetic level. For this, we have compiled a table showing when and where the more than forty regulatory genes thus far identified are expressed during nephrogenesis(this table being a subset of a database also containing information on structural and functional proteins expressed during nephrogenesis). The data on the regulatory genes demonstrate, in particular, the importance of the Wilms' tumour gene, WT1, in nephrogenesis, the growth-stimulating interaction between the hepatocyte growth factor and its receptor, c-met, and the differences between uninduced and induced metanephric mesenchyme. In an attempt to highlight those stable developmental pathways which underpin the formation of the kidney and to facilitate future work, we have identified possible checkpoints occurring during nephrogenesis (stages at which a positive signal is needed for development to continue). The data to hand suggest that such checkpoints occur when metanephric mesenchyme is established in the intermediate mesoderm, when induction takes place, when stem cells are activated and before mesenchyme aggregates to form nephrogenic condensations. We suggest that this information can be used as the basis for subtractive hybridizations to identify further regulatory genes that are expressed as the developing kidney progresses from one checkpoint to the next.