Smad1/Smad5 signaling in limb ectoderm functions redundantly and is required for interdigital programmed cell death

► Canonical Smad1/Smad5 signaling functions redundantly in BMP-regulated AER functions. ► Syndactyly of Smad1/5 mutant: reduction in PCD and increase in cell proliferation. ► The epithelial-mesenchymal interaction regulates the interdigital regression. ► Prolonged Fgf8 expression in Smad1/5 mutants as survival signal to interdigital cells ► Ventral ectoderm thickened after Smad1/5 inactivation and located ectopically dorsal.