Digits V, IV and part of III arise directly from cells that express SHH during embryogenesis. In these cells SHH signals in an autocrine fashion and these digits develop correctly in the absence of DISP, which is required for extracellular diffusion of the ligand. These digits differ in the length of time that SHH continues to be expressed. The most posterior digit V develops from cells that express the ligand for the longest period of time. Digit IV cells express SHH for a shorter time, and digit III cells shorter still. Digit II develops from cells that are exposed to moderate concentrations of extracellular SHH. Finally, Digit I development does not require SHH. It is, in a sense, the default program of limb bud cells.