A Versatile Signal In Vertebrate Embryogenesis: Wnt-4 Regulates Kidney Development, Sex Organ Differentiation, Neuronal Survival And Axonal Guidance

Researchers at the Max Planck Institute for Immunobiology, at Harvard University, at Oulu University /Finland and at the University of California characterised the important signalling role of a secreted protein of the Wnt family in kidney development, sex organ differentiation and axonal growth and guidance in vertebrate embryogenesis. (Development 125, 4225-4234, 1998; Nature 397, 405-409, 1999; Science 283, 1180-1183,1999)

The formation of vertebrate organs is a complex process. It is characterised by the interaction of different cells and tissues to assure the concerted program of cell growth, differentiation and morphogenesis which garanties the functional architecture of the adult organ. Cell and tissue interactions are mediated by signalling molecules of various protein classes.

The mammalian kidney has been widely exploited as a model system to study the principles of vertebrate organ formation. Kidney development is characterized by an interaction between an epithelial and a mesenchymal compartment: the Wolffian duct and the nephrogenic mesenchyme. Dependent on signals from the mesenchyme, the ureter will give rise to the adult collecting duct system whereas the mesenchyme upon signals from the ureter will differentiate to form the major part of the nephrons, the functional unit of the excretory system, which is responsible for removal of nitrogenous waste and physiological control of salt balance.

An important family of signalling molecules is encoded by Wnt genes. Wnt proteins are secreted glycoproteins which have been shown to regulate numerous developmental processes like brain formation, limb patterning, and axis formation in the vertebrate embryo.

Classical experiments demonstrated the reciprocal nature of inductive events in the kidney using tissue separation and recombination techniques. The ureteric bud induces the mesenchyme to condense and to form tubules - precursors to nephrons. The mesenchyme in turn promotes ureteric bud

Contact: Andreas Kispert

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