FIGURE 1. Early signalling steps in specification of embryonic skin.

a, In the absence of Wnt signalling, ectodermal progenitors respond to FGFs, downregulate BMP signalling and progress towards neurogenesis¹. Wnt signalling blocks the ability of early ectodermal progenitor cells to respond to FGFs, allowing them to respond to BMP signalling and adopt an epidermal fate. As development progresses, single-layered embryonic epidermis expresses Wnts. Some cells fail to respond to Wnts, and these become fated to become epidermal cells through BMP, EGF and Notch signalling. The cells that do respond to Wnt signalling also receive underlying FGF and BMP inhibitory signals from the mesenchyme and, together, these signals instruct the cells to make an appendage^{4, 6, 7, 8, 9, 10}. Collectively, the inhibition of BMP inhibitory signals and Wnt activating signals produce the hair placode^{9, 12, 13}. Additional dermal messages from below further instruct the placodes to make the follicle.