title: Planarian Hedgehog/Patched establishes anterior-posterior polarity by regulating Wnt signaling.
abstract: Despite long-standing interest, the molecular mechanisms underlying the establishment of anterior-posterior (AP) polarity remain among the unsolved mysteries in metazoans. In the planarians (a family of flatworms), canonical Wnt/beta-catenin signaling is required for posterior specification, as it is in many animals. However, the molecular mechanisms regulating the posterior-specific induction of Wnt genes according to the AP polarity have remained unclear. Here, we demonstrate that Hedgehog (Hh) signaling is responsible for the establishment of AP polarity via its regulation of the transcription of Wnt family genes during planarian regeneration. We found that RNAi gene knockdown of Dugesia japonica patched (Djptc) caused ectopic tail formation in the anterior blastema of body fragments, resulting in bipolar-tails regeneration. In contrast, RNAi of hedgehog (Djhh) and gli (Djgli) caused bipolar-heads regeneration. We show that Patched-mediated Hh signaling was crucial for posterior specification, which is established by regulating the transcription of Wnt genes via downstream Gli activity. Moreover, differentiated cells were responsible for the posterior specification of undifferentiated stem cells through Wnt/beta-catenin signaling. Surprisingly, Djhh was expressed in neural cells all along the ventral nerve cords (along the AP axis), but not in the posterior blastema of body fragments, where the expression of Wnt genes was induced for posteriorization. We therefore propose that Hh signals direct head or tail regeneration according to the AP polarity, which is established by Hh signaling activity along the body's preexisting nervous system.
authors.affiliation: Department of Biophysics, Division of Biological Sciences, Graduate School of Science, Kyoto University, Kitashirakawa-Oiwake, Sakyo-ku, Kyoto 606-8502, Japan.
authors.forename: Shigenobu
authors.initials: S
authors.lastname: Yazawa
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Umesono
authors.forename: Tetsutaro
authors.initials: T
authors.lastname: Hayashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tarui
authors.forename: Kiyokazu
authors.initials: K
authors.lastname: Agata
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000235:genetics / Q000502:physiology*; D008954:Models, Biological; D008969:Molecular Sequence Data; D000072079:Patched Receptors; D010932:Planarians / Q000235:genetics / Q000254:growth & development* / Q000502:physiology*; D034622:RNA Interference; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D012038:Regeneration / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction; D051153:Wnt Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D053823:Hedgehog Proteins; D000072079:Patched Receptors; D011956:Receptors, Cell Surface; D051153:Wnt Proteins