title: Polarized notum activation at wounds inhibits Wnt function to promote planarian head regeneration.
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.
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
authors.forename: Christian P
authors.initials: CP
authors.lastname: Petersen
authors.forename: Peter W
authors.initials: PW
authors.lastname: Reddien
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D025461:Feedback, Physiological; D005786:Gene Expression Regulation; D017238:Genes, Helminth; D006257:Head; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism*; D006867:Hydrolases / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010932:Planarians / Q000166:cytology / Q000235:genetics / Q000502:physiology*; D034622:RNA Interference; D012038:Regeneration; D015398:Signal Transduction; D013623:Tail; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D051155:Wnt1 Protein / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D015801:Helminth Proteins; D051153:Wnt Proteins; D051155:Wnt1 Protein; D051176:beta Catenin; D006867:Hydrolases