title: Integrin suppresses neurogenesis and regulates brain tissue assembly in planarian regeneration.
abstract: Animals capable of adult regeneration require specific signaling to control injury-induced cell proliferation, specification and patterning, but comparatively little is known about how the regeneration blastema assembles differentiating cells into well-structured functional tissues. Using the planarianSchmidtea mediterraneaas a model, we identifyβ1-integrinas a crucial regulator of blastema architecture.β1-integrin(RNAi)animals formed small head blastemas with severe tissue disorganization, including ectopic neural spheroids containing differentiated neurons normally found in distinct organs. By mimicking aspects of normal brain architecture but without normal cell-type regionalization, these spheroids bore a resemblance to mammalian tissue organoids synthesizedin vitroWe identified one of four planarian integrin-alpha subunits inhibition of which phenocopied these effects, suggesting that a specific receptor controls brain organization through regeneration. Neoblast stem cells and progenitor cells were mislocalized inβ1-integrin(RNAi)animals without significantly altered body-wide patterning. Furthermore, tissue disorganization phenotypes were most pronounced in animals undergoing brain regeneration and not homeostatic maintenance or regeneration-induced remodeling of the brain. These results suggest that integrin signaling ensures proper progenitor recruitment after injury, enabling the generation of large-scale tissue organization within the regeneration blastema.
authors.affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA.
authors.forename: Nicolle A
authors.initials: NA
authors.lastname: Bonar
authors.affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA christian-p-petersen@northwestern.edu.|Robert Lurie Comprehensive Cancer Center, Northwestern University, Evanston, IL 60208, USA.
authors.forename: Christian P
authors.identifier: 0000-0001-7552-6865
authors.initials: CP
authors.lastname: Petersen
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics; D001921:Brain / Q000502:physiology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D018507:Gene Expression Regulation, Developmental; D019012:Integrin beta1 / Q000502:physiology*; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology; D010932:Planarians / Q000502:physiology*; D034622:RNA Interference; D012038:Regeneration; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology*
chemical_list: D019012:Integrin beta1
keywords: Blastema; Brain regeneration; Integrin; Morphogenesis; Organoids; Planaria