MOLECULAR DEVELOPMENT OF THE KIDNEY - A REVIEW OF THE RESULTS OF GENEDISRUPTION STUDIES

The kidney has been used for the last 50 years as a model system for t he study of tissue inductions and vertebrate organogenesis. While much is known about the morphologic development of the kidney, it is only in the last few years that the molecular mechanisms involved in these processes have begun to be identified. This is largely a result of the identification of genes expressed during kidney development and the a pplication of techniques for single gene disruption. Mammalian kidney development is described, and the methodology for single gene disrupti on is discussed. For a candidate gene to be unequivocally shown to be involved in organ development, three conditions are necessary. First, the gene must be spatially expressed correctly relative to the develop ing organ, Second, the gene has to be temporally expressed in a correc t manner, Finally, when that gene is disrupted, normal organ developme nt must not occur. There are now 11 genes that satisfy these condition s and thus have been shown to be crucial for metanephric kidney develo pment: WT-I, Pax-2, c-ret, GDNF, alpha 8 beta 1, Wnt-4, BF-2, BMP-7, P DGFB, PDGFR beta, and alpha 3 beta 1. These genes and their probable r oles in kidney development are discussed, and some molecular pathways are suggested. Finally, the applications, limitations, and future tren ds in single gene disruption studies are discussed. Single gene disrup tion already has generated a wealth of information about kidney develo pment and mammalian development in general. It is likely that this inf ormation is only the beginning, and many startling and profound discov eries can be expected in the years to come both from the utilization o f knockout mice that already exist and those that will be created. (C) 1998 by the National Kidney Foundation, Inc.