Mice overexpressing ShhN (Sox2-Cre;Shh+/+;ShhN or Sox2-Cre;ShhF/F;ShhN) exhibit polydactyly, holoprosencephaly, and cleft palate due to the long-range spread and activation of Shh signaling [24,25]. This evidence concerns the gene SOX2 and holoprosencephaly.