Glial cell line-derived neurotrophic factor (GDNF) is expressed in the metanephric mesenchyme during formation of the ureteric bud (inferred from mouse embryos). GDNF, which is secreted from the metanephric mesenchyme, interacts with the RET receptor tyrosine kinase on the nephric duct epithelium to regulate induction of the ureteric bud (inferred from mouse homologs). Mice lacking Gdnf fail to develop kidneys (Pichel et al. 1996). Based on phenotypes of gene knockouts in mice, Slit2 and Robo2 appear to repress Gdnf expression to limit the size of the ureteric bud (Grieshammer et al. 2004), however this may be an indirect effect produced by the activity of Slit2:Robo2 in producing normal physical separation of the mesenchyme from the Wolffian duct (mesonephric duct) and the ureteric epithelium (Wainwright et al. 2015). In mouse embryos, Foxc1 and Foxc2 from the paraxial mesoderm inhibit expression of Gdnf to limit the anterior extent of kidney development (Kume et al. 2000).