Extended Data Fig. 10 |. Controlled mechanical advancement of the lower jaw unlocks neural crest potential for regeneration of the mandible.

a, At the tissue level, clonality within the mandible during distraction (middle) is observed to occur in a highly linear and directional manner in parallel to the vector of distraction. By contrast, clonality observed in fracture (top) and distraction plus FAKi (bottom) was highly mesenchymal with less apparent organization in its morphology, indicating a nondirectional clonal proliferation. b, The cellular level: the developmental origin of the NCC-derived SSCs of the mandible (top), and the postnatal SSCs of the mandible (bottom) that are present in our experiments. During distraction the d-SSC (shown in pink) demonstrates plasticity and takes on an NCC- derived signature, whereas the f-SSC (purple) retains its postnatal SSC characteristics with no NCC signature. In the absence of FAK signalling, the d-SSC FAKi (green) reverts functionally and epigenomically to the fracture state without emergence of the NCC signature. ‘NCC Prog’ indicates the premigratory (e8.5) NCC progenitor population; ‘NCC Md’ indicates the postmigratory (e10.5) NCC population arriving within the mandible. c, At the chromatin level, distraction induces a gain in accessibility at promoters (P) of FAK-responsive NCC craniofacial genes through the activation of their enhancers (E), with a parallel gain in accessibility of retroviral elements near NCC-specific craniofacial enhancers. Thus mechanotransduction during mandible distraction unlocks FAK-responsive craniofacial enhancers, potentially through retrotransposons, enacting a developmental NCC program in d-SSCs similar to that of the e10.5 NCC Md population (b). This does not occur under fracture conditions (top) or during distraction plus FAKi (bottom). These differential epigenomic responses correlate with the degree of clonality and patterning seen in Rainbow mice (a) that occurs in response to distraction. Circled P represents phosphorylation.