 Grem1 inhibits predominantly BMP2 and BMP4 in limb buds and functions as part of a self-regulatory feedback signaling system, which is essential for normal limb bud development and digit formation.Inhibition of BMPs by Grem1 in limb buds allows the transcriptional up-regulation of the fibroblast growth factors (FGFs) 4 and 8 and sonic hedgehog (SHH) ligands, which are part of the signaling system that controls progression of limb bud development.Grem1 regulation of BMP4 in mice embryos is also essential for kidney and lung branching morphogenesis.