Sonic hedgehog (Shh) signalling is a key player in vertebrate development,patterning structures ranging from the nervous system to the limb. It is also crucial for the morphogenesis of the epithelial lining of the mouth and of the respiratory and gut tubes in mice. Here, on , Toshihiko Shiroishi and co-workers identify long-range enhancers that regulate regional Shh expression in the epithelial lining and demonstrate their developmental function. By comparing genomic sequences across mammals and teleost fish, the authors identify three conserved non-coding sequences(CNCSs) upstream of the Shh coding region, which together recapitulate Shh expression in the epithelial lining of the oral cavity, pharynx, lung and gut. To examine the function of CNCSs in vivo, the researchers deleted the one that drives pharyngeal Shh expression and report that this results in the severe underdevelopment of pharyngeal structures, such as the soft palate. These results indicate that the three long-range Shh enhancers partition the epithelial lining into three domains and are required for proper epithelial morphogenesis.
