Sonic hedgehog signaling pathway in vertebrate epithelial appendage morphogenesis: perspectives in development and evolution

Vertebrate epithelial appendages are elaborate topological transformations of flat epithelia into complex organs that either protrude out of external (integument) and internal (oral cavity, gut) epithelia, or invaginate into the surrounding mesenchyme. Although they have specific structures and dive rse functions, most epithelial appendages share similar developmental stage s, including induction, morphogenesis, differentiation and cycling. The rol es of the SHH pathway are analyzed in exemplary organs including feather, h air, tooth, tongue papilla, lung and foregut. SHH is not essential for indu ction and differentiation, but is involved heavily in morphogenetic process es including cell proliferation (size regulation), branching morphogenesis, mesenchymal condensation, fate determination (segmentation), polarizing ac tivities and so oil. Through differential activation of these processes by SHH in a spatiotemporal-specific fashion, organs of different shape and siz e are laid down. During evolution, new links of developmental pathways may occur and novel for ms of epithelial appendages may emerge, upon which evol utionary selections call act. Sites of major variations have progressed fro m the body plan to the limb plan to the epithelial appendage plan. With its powerful morphogenetic activities, the SHH pathway would likely continue t o play a major role in the evolution of novel epithelial appendages.