SIX3 and holoprosencephaly: In conclusion, Six3 or Shh null animals show a severe holoprosencephalic phenotype (with cyclopia), while diminishing variations in Shh and Six3 levels result in septo-optic dysplasia or holoprosencephaly, respectively, with different degrees of severity (Jeong et al., 2008; Geng et al., 2016).