suppresses terminal differentiation of migratory eye progenitors in planarian regeneration.

Proper stem cell targeting and differentiation is necessary for regeneration to succeed. In organisms capable of whole body regeneration, considerable progress has been made identifying wound signals initiating this process, but the mechanisms that control the differentiation of progenitors into mature organs are not fully understood. Using the planarian as a model system, we identify a novel function for , a MAP3K family member possessing both kinase and ubiquitin ligase domains, to negatively regulate terminal differentiation of stem cells during eye regeneration. Inhibition of caused the formation of multiple ectopic eyes within the head, but without controlling overall head, brain, or body patterning. By contrast, other known regulators of planarian eye patterning like and also regulate head regionalization, suggesting acts distinctly. Eye resection and regeneration experiments suggest that unlike Wnt signaling perturbation, inhibition did not shift the target destination of eye formation in the animal. Instead, ectopic eyes emerge in the regions normally occupied by migratory eye progenitors, and the onset of ectopic eyes after inhibition coincides with a reduction to eye progenitor numbers. Furthermore, RNAi dosing experiments indicate that progenitors closer to their normal target are relatively more sensitive to the effects of , implicating this factors in controlling the site of terminal differentiation. Eye phenotypes were also observed after inhibition of , and , identifying a putative pathway through which prevents differentiation. Together, these results suggest that regulates a novel control point in the eye regeneration pathway which suppresses the terminal differentiation of progenitors during their migration to target destinations.