SLIT2-mediated ROBO2 signaling restricts kidney induction to a single site

Kidney development occurs in a stereotypic position along the body axis. It begins when a single ureteric bud emerges from the nephric duct in response to GDNF secreted by the adjacent nephrogenic mesenchyme. Posterior restriction of Gdnf expression is considered critical for correct positioning of ureteric bud development. Here we show that mouse mutants lacking either SLIT2 or its receptor ROBO2, molecules known primarily for their function in axon guidance and cell migration, develop supernumerary ureteric buds that remain inappropriately connected to the nephric duct, and that the SLIT2/ROBO2 signal is transduced in the nephrogenic mesenchyme. Furthermore, we show that Gdnf expression is inappropriately maintained in anterior nephrogenic mesenchyme in these mutants. Thus our data identify an intercellular signaling system that restricts, directly or indirectly, the extent of the Gdnf expression domain, thereby precisely positioning the site of kidney induction.