title: The molecular logic for planarian regeneration along the anterior-posterior axis.
abstract: The planarian Dugesia japonica can regenerate a complete individual from a head, trunk or tail fragment via activation of somatic pluripotent stem cells. About a century ago, Thomas Hunt Morgan attempted to explain the extraordinary regenerative ability of planarians by positing two opposing morphogenetic gradients of formative "head stuff" and "tail stuff" along the anterior-posterior axis. However, Morgan's hypothesis remains open to debate. Here we show that extracellular signal-related kinase (ERK) and Wnt/β-catenin signalling pathways establish a solid framework for planarian regeneration. Our data suggest that ERK signalling forms a spatial gradient in the anterior region during regeneration. The fibroblast growth factor receptor-like gene nou-darake (which serves as an output of ERK signalling in the differentiating head) and posteriorly biased β-catenin activity negatively regulate ERK signalling along the anterior-posterior axis in distinct manners, and thereby posteriorize regenerating tissues outside the head region to reconstruct a complete head-to-tail axis. On the basis of this knowledge about D. japonica, we proposed that β-catenin signalling is responsible for the lack of head-regenerative ability of tail fragments in the planarian Phagocata kawakatsui, and our confirmation thereof supports the notion that posterior β-catenin signalling negatively modulates the ERK signalling involved in anteriorization across planarian species. These findings suggest that ERK signalling has a pivotal role in triggering globally dynamic differentiation of stem cells in a head-to-tail sequence through a default program that promotes head tissue specification in the absence of posteriorizing signals. Thus, we have confirmed the broad outline of Morgan's hypothesis, and refined it on the basis of our proposed default property of planarian stem cells.
authors.affiliation: RIKEN Center for Developmental Biology, Kobe 650-0047, Japan. umesono.yoshihiko@tokushima-u.ac.jp
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Umesono
authors.forename: Junichi
authors.initials: J
authors.lastname: Tasaki
authors.forename: Yui
authors.initials: Y
authors.lastname: Nishimura
authors.forename: Martina
authors.initials: M
authors.lastname: Hrouda
authors.forename: Eri
authors.initials: E
authors.lastname: Kawaguchi
authors.forename: Shigenobu
authors.initials: S
authors.lastname: Yazawa
authors.forename: Osamu
authors.initials: O
authors.lastname: Nishimura
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Hosoda
authors.forename: Takeshi
authors.initials: T
authors.lastname: Inoue
authors.forename: Kiyokazu
authors.initials: K
authors.lastname: Agata
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000187:drug effects / Q000502:physiology*; D002454:Cell Differentiation; D015536:Down-Regulation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D025461:Feedback, Physiological; D006257:Head / Q000502:physiology; D008128:Logic; D020935:MAP Kinase Signaling System / Q000187:drug effects; D010641:Phenotype; D010932:Planarians / Q000033:anatomy & histology* / Q000187:drug effects / Q000502:physiology*; D017468:Receptors, Fibroblast Growth Factor / Q000737:chemistry / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism
chemical_list: D017468:Receptors, Fibroblast Growth Factor; D051153:Wnt Proteins; D051176:beta Catenin; D048049:Extracellular Signal-Regulated MAP Kinases