During kidney development, unknown signals derived from the ureteric b
ud induce metanephric mesenchymal cells to differentiate into nephron
epithelia. In addition to the ureteric bud, a number of other tissues
can act as heterologous inducers of this process in vitro, including e
mbryonic spinal cord. In this report we demonstrate that Wnt-1, a gene
that encodes a secreted glycoprotein expressed in embryonic spinal co
rd, is capable of conferring nephron-inducing activity to fibroblast c
ell lines. When cocultured with cells expressing exogenous Wnt-1, meta
nephric mesenchyme differentiated into glomerular and renal tubular ep
ithelia. No such effect was observed using control cells. These data i
mply that the ability of embryonic spinal cord to act as an inducer of
nephrogenesis may result from its production of Wnt-1 protein and sug
gest that a member of the Wnt gene family may be a mediator of renal e
pithelial morphogenesis in vivo. (C) 1994 Academic Press, Inc.