Sonic hedgehog is required for neural crest-dependent patterning of the intrinsic tongue musculature

The tongue is a highly specialized muscular organ important for breathing, speech, taste and swallowing. The secreted signaling molecule Sonic hedgehog (Shh) is expressed in dorsal tongue epithelium from the initial developmental stage. In this study, we utilized a series of genetic approaches to investigate the role of Shh during mouse tongue formation. Temporal-specific global deletion of Shh demonstrated a functional requirement for normal patterning of the intrinsic tongue muscles and establishment of the lingual tendon. These defects were reproduced in the mutant with a specific loss of signaling in oropharyngeal epithelium by a Shh cis-enhancer. In these mutants, Ptch1 was lost in the underlying cranial neural crest (CNC)-derived mesenchymal lineage. The importance of Shh was confirmed by generating tissue-specific deletions in the ciliopathy gene Ofd1, which transduces Shh signaling. These results revealed Shh roles in patterning of the mesodermal intrinsic tongue muscles through CNC-derived mesenchyme, including the lingual tendon.