SHH and ciliopathy: Dysregulation of the Shh pathway is linked to craniofacial malformations such as holoprosencephaly in genetic ciliopathies (Brugmann et al., 2015; Chang et al., 2016), and PAE both downregulates Shh expression (Higashiyama et al., 2007) and causes more severe craniofacial and limb defects in transgenic mice lacking genes in the Shh pathway (Fish et al., 2017; Kietzman et al., 2014).