SHH and polydactyly: HOX genes, hedgehog pathways (sonic Hedgehog (SHH) and Indian Hedgehog (IHH), FGFs, bone morphogenetic proteins, and cartilage-derived morphogenetic proteins all play a significant role in limb development.[44] The SHH signaling system is essential for limb development.[45] 15 SHH is influenced by or influences various transcription factors, including HAND2, GLI3, ALX4, and some bone morphogenetic proteins antagonists (formin and gremlin), alterations which have resulted in polydactyly.