title: zic-1 Expression in Planarian neoblasts after injury controls anterior pole regeneration.
abstract: 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.
authors.affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, Illinois, United States of America.
authors.forename: Constanza
authors.initials: C
authors.lastname: Vásquez-Doorman
authors.affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, Illinois, United States of America; Robert Lurie Comprehensive Cancer Center, Northwestern University, Evanston, Illinois, United States of America.
authors.forename: Christian P
authors.initials: CP
authors.lastname: Petersen
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D018507:Gene Expression Regulation, Developmental; D006257:Head / Q000254:growth & development; D015801:Helminth Proteins / Q000235:genetics*; D010932:Planarians / Q000235:genetics; D039904:Pluripotent Stem Cells; D012038:Regeneration / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*; D013623:Tail / Q000254:growth & development; D014157:Transcription Factors; D051153:Wnt Proteins / Q000235:genetics*
chemical_list: D015801:Helminth Proteins; D014157:Transcription Factors; D051153:Wnt Proteins