Which molecule is essential for interdigital apoptosis in tetrapod limbs?
Digit separation requires selective elimination of interdigital necrotic zones by programmed cell death. BMP ligands through BMPR1A BMPR1B activate phosphorylated Smad1-5-8 cascade, transcriptionally upregulate Msx1 Msx2 and promote caspase-dependent apoptosis with DNA fragmentation. Distal FGFs from digit tips antagonize BMP to protect digit chondrogenesis driven by Sox9. In ducks, Gremlin blocks BMP and retains webbing; ectopic Noggin in chick creates syndactyly. Genetic ablation of BMP2 or BMP4 or Msx2 causes soft-tissue fusion. SHH and FGF10 promote growth, RA modulates proximal identity, but BMP4 execution is central to interdigital apoptosis forming free digits.
Ref: Gilbert, Developmental Biology, 12th ed., Chapter 20: BMP-induced interdigital apoptosis.