Lack of specificity of planarian progenitor responses to injury in regeneration.

Regeneration is the process by which organisms replace lost body parts. How cell-type production is tailored to match the identity of missing tissues is a central problem of regeneration. Here, we investigated the specificity of planarian stem-cell responses to the identity of missing tissues following injury. Proximal injury not affecting the mature tissue nonetheless drives increased cell incorporation into brain neurons, ventral nerve cords, pharynx muscle and neurons. Following direct injury, peripheral neurons show a spatially imprecise, generic amplification of incorporation relative to the injury; body-wall muscle incorporation was amplified, with decreased incorporation at wound-distal sites in favor of increased incorporation wound-proximally. By contrast, essentially no stem-cell division contributes to initial epidermal regeneration, instead post-mitotic progenitors supply the wound. Amplification of epidermal incorporation following injury does occur weeks after injury, including to uninjured regions. These results indicate that the identity of the missing mature tissue is not required in determining the stem-cell response to injury. We suggest that planarian regeneration specificity involves a combination of ongoing cell turnover, wound-associated amplification of stem-cells, and spatially broad neoblast specification zones.