Zebrafish can fully regenerate their fins, a process that involves the reconstitution and patterning of multiple tissue types. New bone is regenerated via the de-differentiation, proliferation and re-differentiation of osteoblasts, which occur in a spatially organised manner to recapitulate the original fin shape and skeleton. How skeletal patterning – including outgrowth and bifurcation of new rays – is controlled in this context is incompletely understood, though is thought to involve Hedgehog signalling. Kryn Stankunas, Scott Stewart and colleagues (p. 1165) now define distinct roles for the two Hedgehog ligands expressed in the regenerating fin: shha and ihha. shha is expressed in epidermal cells immediately adjacent to osteoblasts at the site of ray branching, and is required for branching. Intriguingly, it appears to act at short range, through direct contact with osteoblast progenitors via cellular protrusions, to promote splitting of the ray through cell movements. ihha, on the other hand, is expressed in the osteoblasts, where it promotes differentiation via a non-canonical signalling route. These data clarify the role of Hedgehog signalling in ray regeneration and shed light onto the mechanisms underlying skeletal patterning in regenerative contexts.
