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Polarized notum Activation at Wounds Inhibits Wnt Function to Promote Planarian Head Regeneration
Christian P. Petersen1,*, and
Peter W. Reddien1,2,3,
Abstract:
Regeneration requires initiation of programs tailored to the identity of missing parts. Head-versus-tail regeneration in planarians presents a paradigm for study of this phenomenon. After injury, Wnt signaling promotes tail regeneration. We report that wounding elicits expression of the Wnt inhibitor notum preferentially at anterior-facing wounds. This expression asymmetry occurs at essentially any wound, even if the anterior pole is intact. Inhibition of notum with RNA interference (RNAi) causes regeneration of an anterior-facing tail instead of a head, and double-RNAi experiments indicate that notum inhibits Wnt signaling to promote head regeneration. notum expression is itself controlled by Wnt signaling, suggesting that regulation of feedback inhibition controls the binary head-tail regeneration outcome. We conclude that local detection of wound orientation with respect to tissue axes results in distinct signaling environments that initiate appropriate regeneration responses.
1 Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA. 2 Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02138, USA. 3 Howard Hughes Medical Institute, 4000 Jones Bridge Road, Chevy Chase, MD 20815, USA.
* Present address: Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA.
To whom correspondence should be addressed. E-mail: reddien{at}wi.mit.edu
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