Editors' ChoiceRegeneration

Snips and Tales of Planarian Tails

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Science Signaling  17 May 2011:
Vol. 4, Issue 173, pp. ec139
DOI: 10.1126/scisignal.4173ec139

Much is known about the establishment of body axes in embryos, but the establishment of polarity in regenerating tissues is less well understood. Planaria exhibit remarkable regenerative abilities, including the ability to regenerate missing heads or tails, or both simultaneously, in the correct orientation with respect to the main body axis. Wnt signaling promotes tail formation, whereas inhibitors of Wnt signaling promote head formation. Expression of wnt1 is induced at both anterior and posterior wounds, yet only posterior-facing wounds regrow a tail. Petersen and Reddien report that Wnt signaling in anterior-facing wounds is repressed by Notum, an α/β-hydrolase that inhibits Wnt signaling in fruit flies by cleaving the glycosylphosphatidylinositol anchors required for glypicans to promote Wnt signaling. notum was expressed in anterior-facing but not posterior-facing wounds at any location along the anteroposterior axis, both when the cut resulted in tissue amputation and when an incision was made without removing tissue. When two cuts perpendicular to the anteroposterior axis were located near one another, notum was expressed more robustly in the more posterior of the two anterior-facing wound edges, suggesting that the presence of a posterior-facing wound repressed notum expression in the other anterior-facing wound. Reducing notum expression by RNA interference (RNAi) blocked the ability to regenerate heads but not the ability to regenerate tails. Regenerated anterior tissue in notum RNAi-treated planaria exhibited tail characteristics, including posterior gut morphology and the absence of photoreceptors and cephalic ganglia. Expression of wntP-2, which requires the activity of Wnt1 and the Wnt signaling effector β-catenin, was increased at posterior-facing but not anterior-facing wounds. Genetics experiments indicated that notum expression depended upon Wnt1 and β-catenin, and Notum acted as a feedback inhibitor of Wnt signaling. The factors that inhibit notum expression at posterior-facing wounds have not been identified. The function of Notum has not been elucidated outside of the fruit fly, but the conservation of Notum from sea anemones to humans and the prevalence of Wnt signaling in regeneration across species suggest that Notum may play a more general role in determining regeneration polarity. A Perspective by Slack considers these results within the broader context of tissue regeneration and discusses new findings from an accompanying paper by Wagner et al. that demonstrates the pluripotent nature of neoblasts, the planarian equivalent of adult stem cells.

C. P. Petersen, P. W. Reddien, Polarized notum activation at wounds inhibits Wnt function to promote planarian head regeneration. Science 332, 852–855 (2011). [Abstract] [Full Text]

D. E. Wagner, I. E. Wang, P. W. Reddien, Clonogenic neoblasts are pluripotent adult stem cells that underlie planarian regeneration. Science 332, 811–816 (2011). [Abstract] [Full Text]

J. M. W. Slack, Planarian pluripotency. Science 332, 799–800 (2011). [Abstract] [Full Text]

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