Shh signaling directs dorsal ventral patterning in the regenerating spinal cord.

Tissue development and regeneration rely on the deployment of embryonic signals to drive progenitor activity and thus generate complex cell diversity and organization. One such signal is Sonic Hedgehog (Shh), which establishes the dorsal-ventral (D/V) axis of the spinal cord during embryogenesis. However, the existence of this D/V axis and its dependence on Shh signaling during regeneration varies by species. Here we investigate the function of Shh signaling in patterning the D/V axis during spinal cord regeneration in tadpoles. We find that neural progenitor markers Msx1/2, Nkx6.1, and Nkx2.2 are confined to dorsal, intermediate and ventral spatial domains, respectively, in both the uninjured and regenerating spinal cord. These domains are altered by perturbation of Shh signaling. Additionally, we find that these D/V domains are more sensitive to Shh perturbation during regeneration than uninjured tissue. The renewed sensitivity of these neural progenitor cells to Shh signals represents a regeneration specific response and raises questions about how responsiveness to developmental patterning cues is regulated in mature and regenerating tissues.