title: β-Catenin inactivation is a pre-requisite for chick retina regeneration.
abstract: In the present study we explored the role of β-catenin in mediating chick retina regeneration. The chick can regenerate its retina by activating stem/progenitor cells present in the ciliary margin (CM) of the eye or via transdifferentiation of the retinal pigmented epithelium (RPE). Both modes require fibroblast growth factor 2 (FGF2). We observed, by immunohistochemistry, dynamic changes of nuclear β-catenin in the CM and RPE after injury (retinectomy). β-Catenin nuclear accumulation was transiently lost in cells of the CM in response to injury alone, while the loss of nuclear β-catenin was maintained as long as FGF2 was present. However, nuclear β-catenin positive cells remained in the RPE in response to injury and were BrdU-/p27+, suggesting that nuclear β-catenin prevents those cells from entering the cell cycle. If FGF2 is present, the RPE undergoes dedifferentiation and proliferation concomitant with loss of nuclear β-catenin. Moreover, retinectomy followed by disruption of active β-catenin by using a signaling inhibitor (XAV939) or over-expressing a dominant negative form of Lef-1 induces regeneration from both the CM and RPE in the absence of FGF2. Our results imply that β-catenin protects cells of the CM and RPE from entering the cell cycle in the developing eye, and specifically for the RPE during injury. Thus inactivation of β-catenin is a pre-requisite for chick retina regeneration.
authors.affiliation: Department of Biology, Miami University, Oxford, Ohio, United States of America.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Biology, Miami University, Oxford, Ohio, United States of America.
authors.forename: Agustin
authors.initials: A
authors.lastname: Luz-Madrigal
authors.affiliation: Department of Biology, Miami University, Oxford, Ohio, United States of America.
authors.forename: Tracy
authors.initials: T
authors.lastname: Haynes
authors.affiliation: Department of Biology, Miami University, Oxford, Ohio, United States of America.
authors.forename: Julia
authors.initials: J
authors.lastname: Zavada
authors.affiliation: Department of Biology, Miami University, Oxford, Ohio, United States of America.
authors.forename: Amy K
authors.initials: AK
authors.lastname: Burke
authors.affiliation: Department of Biology, Miami University, Oxford, Ohio, United States of America.
authors.forename: Katia
authors.initials: K
authors.lastname: Del Rio-Tsonis
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D002642:Chick Embryo; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006575:Heterocyclic Compounds, 3-Ring / Q000494:pharmacology; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D021381:Protein Transport; D012038:Regeneration; D012160:Retina / Q000166:cytology / Q000187:drug effects / Q000196:embryology / Q000502:physiology*; D055213:Retinal Pigment Epithelium / Q000196:embryology / Q000502:physiology; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D051820:TCF Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D060449:Wnt Signaling Pathway / Q000187:drug effects; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D006575:Heterocyclic Compounds, 3-Ring; D051821:Lymphoid Enhancer-Binding Factor 1; D055748:SOXB1 Transcription Factors; D051820:TCF Transcription Factors; C544261:XAV939; D051176:beta Catenin; D016222:Fibroblast Growth Factor 2