SHH and holoprosencephaly: Mice with targeted disruption of Shh have alobar HPE and cyclopia (Chiang et al., 1996); whilst in humans, mutation in a number of pathway components have been associated with various forms of HPE, including SHH itself (Belloni et al., 1996; Roessler et al., 1996), PTCH1 (Ming et al., 2002), the upstream transmembrane protein DISPATCHED-1 (DISP1) (Roessler et al., 2009) and the downstream transcription factor GLI2 (Roessler et al., 2003).