Sonic hedgehog and fibroblast growth factor 8 regulate the evolution of amniote facial proportions

Amniote skulls are diverse in shape and skeletal composition, which is the basis of much adaptive diversification within this clade. Major differences in skull shape are established early in development, at a critical developmental interval spanning the initial outgrowth and fusion of the facial processes. In birds, this is orchestrated by domains of Shh and Fgf8 expression, known as the frontonasal ectodermal zone (FEZ). It is unclear whether this model of facial development applies to species with diverse facial skeletons, especially species possessing a skull morphology representative of early amniotes. By investigating facial morphogenesis in the lizard, Anolis sagrei, we show that reptilian skull development is driven by the same genes as mammals and birds, but the manner in which those genes regulate facial development is clade-specific. These genes are not expressed in the frontal-nasal prominence, the region of the avian FEZ. Downregulating Shh and Fgf8 signaling disrupts normal facial development, but in pathway-specific ways. Our results demonstrate that early facial morphogenesis in lizards does not conform to the FEZ model. Lizard skull development may be more representative of the ancestral amniote than other model species with highly derived facial skeletons suggesting that the FEZ may be an avian-specific novelty.