Model Systems for the Study of Kidney Development: Use of the Pronephros in the Analysis of Organ Induction and Patterning

Abstract

Most vertebrate organs, once formed, continue to perform the function for which they were generated until the death of the organism. The kidney is a notable exception to this rule. Vertebrates, even those that do not undergo metamorphosis, utilize a progression of more complex kidneys as they grow and develop. This is presumably due to the changing conditions to which the organism must respond to retain what Homer Smith referred to as our physiological freedom. To quote, "Recognizing that we have the kind of blood we have because we have the kind of kidneys we have, we must acknowledge that our kidneys constitute the major foundation of our physiological freedom. Only because they work the way they do has it become possible for us to have bones, muscles, glands, and brains. Superficially, it might be said that the function of the kidneys is to make urine; but in a more considered view one can say that the kidneys make the stuff of philosophy itself" ("From Fish to Philosopher," Little, Brown and Co., Boston, 1953). Different kidneys are used to make the stuff of philosophy at different stages of development depending on the age and needs of the organism, rather than the usual approach of simply making embryonic organs larger as the animal grows. Although evolution has provided the higher vertebrates with complex adult kidneys, they continue to utilize simple kidneys in embryogenesis. In lower vertebrates with simple adult kidneys, even more simple versions are used during early developmental stages. In this review the anatomy, development, and gene expression patterns of the embryonic kidney, the pronephros, will be described and compared to the more complex kidney forms. Despite some differences in anatomy, similar developmental pathways seem to be responsible for the induction and the response to induction in both evanescent and permanent kidney forms. Gene expression patterns can, therefore, be added to the morphological and functional data indicating that all forms of the kidney are closely related structures. Given the similarities between the development of simple and complex kidneys, the embryonic kidneys may be an ideal model system in which to investigate the genesis of multicomponent organ systems.

The mutated human gene encoding hepatocyte nuclear factor 1β inhibits kidney formation in developing Xenopus embryos

“…The attractiveness of the Xenopus pronephros as a simple model for the genesis of the vertebrate excretory system relies mainly on the fact that it represents a single nephron and, thus, the basic unit of the successive renal vertebrate organs, i.e., mesonephros and metanephros (27,39). Furthermore, the developing pronephros easily can be monitored in Xenopus as exemplified in our study.…”

Distinct Molecular and Morphogenetic Properties of Mutations in the Human HNF1β Gene That Lead to Defective Kidney Development

“…The anatomy of the Xenopus pronephros is simple in comparison with the human metanephros, but the basic structures are similar and essentially the same regulators are expressed (11)(12)(13)(14). From in situ hybridization, it is known that HNF1␤ is expressed in the pronephros anlage before any cellular differentiation (32) and thus is among the first regulators of nephrogenesis, including lim1 and Pax8 (13,14).…”

“…All three kidneys have the same basic functional unit, the nephron, and similar mechanisms and regulatory genes are involved in nephrogenesis (11,12). In amphibians, the pronephros is the functional kidney throughout larval development, and the frog Xenopus laevis is most attractive to analyze the molecular and cellular events in pronephros formation (13,14).…”

Cell fate specification along the anterior–posterior axis of the intermediate mesoderm

“…Whereas the pronephros appears to arise de novo from cells in the IM, the mesonephros arises along the course of the nephric duct and the metanephros is generated by mutual inductions between duct and mesenchyme (Goodrich, 1930;Saxén, 1987). Recently, it has been shown that expression patterns and the function of many genes that characterize metanephric development appear to be conserved in pronephros development, including Lim-1, Pax-2, Pax-8, WT-1, Sim-1, c-ret, and Wnt-4 (Vize et al, 1997;Chan and Asashima, 2000;Kuure et al, 2000;Jones, 2003).…”