Using LOF and GOF approaches in vivo and in vitro, they show persistent Bmp signaling is the underlying cause of the observed Grem1 phenotype (no ureteric bud outgrowth). Specifically, they demonstrate Bmp4 as the ligand involved.They limit the molecular assay to very few markers. The genetic and culture data is very convincing. Reduced gene dosage of Bmp4 rescue the Grem1 mutant phenotype of no outgrowth. The bmp antogonist Noggin has the same affect, showing targeted reduction of bmp signaling is a general mechanism in this context.