Mechanisms that enable injury responses to prompt regenerative outgrowth are not 
well understood. Planarians can regenerate essentially any tissue removed by 
wounding, even after decapitation, due to robust regulation of adult pluripotent 
stem cells of the neoblast population. Formation of pole signaling centers 
involving Wnt inhibitors or Wnt ligands promotes head or tail regeneration, 
respectively, and this process requires the use of neoblasts early after injury. 
We used expression profiling of purified neoblasts to identify factors needed 
for anterior pole formation. Using this approach, we identified zic-1, a 
Zic-family transcription factor, as transcriptionally activated in a 
subpopulation of neoblasts near wound sites early in head regeneration. As head 
regeneration proceeds, the Wnt inhibitor notum becomes expressed in the newly 
forming anterior pole in zic-1-expressing cells descended from neoblasts. 
Inhibition of zic-1 by RNAi resulted in a failure to express notum at the 
anterior pole and to regenerate a head, but did not affect tail regeneration. 
Both injury and canonical Wnt signaling inhibition are required for zic-1 
expression, and double-RNAi experiments suggest zic-1 inhibits Wnt signaling to 
allow head regeneration. Analysis of neoblast fate determinants revealed that 
zic-1 controls specification of notum-expressing cells from foxD-expressing 
neoblasts to form the anterior pole, which organizes subsequent outgrowth. 
Specialized differentiation programs may in general underlie injury-dependent 
formation of tissue organizing centers used for regenerative outgrowth.