Although the precise nature of the epidermal placode-inducing “first dermal message” remains poorly understood, several studies have suggested that HF initiation is an orchestrated interaction between mesenchymal and epithelial cells mediated through the secretion of stimulator and inhibitor signaling molecules, such as Wnt/β-catenin, EDA/EDAR/NF-κB, Noggin/Lef-1, Shh, BMP-2/4/7 and FGF [9, 14]. This evidence concerns the gene SHH and hydrops fetalis.