title: Surface topography during neural stem cell differentiation regulates cell migration and cell morphology.
abstract: We sought to determine the contribution of scaffold topography to the migration and morphology of neural stem cells by mimicking anatomical features of scaffolds found in vivo. We mimicked two types of central nervous system scaffolds encountered by neural stem cells during development in vitro by constructing different diameter electrospun polycaprolactone (PCL) fiber mats, a substrate that we have shown to be topographically similar to brain scaffolds. We compared the effects of large fibers (made to mimic blood vessel topography) with those of small-diameter fibers (made to mimic radial glial process topography) on the migration and differentiation of neural stem cells. Neural stem cells showed differential migratory and morphological reactions with laminin in different topographical contexts. We demonstrate, for the first time, that neural stem cell biological responses to laminin are dependent on topographical context. Large-fiber topography without laminin prevented cell migration, which was partially reversed by treatment with rock inhibitor. Cell morphology complexity assayed by fractal dimension was inhibited in nocodazole- and cytochalasin-D-treated neural precursor cells in large-fiber topography, but was not changed in small-fiber topography with these inhibitors. These data indicate that cell morphology has different requirements on cytoskeletal proteins dependent on the topographical environment encountered by the cell. We propose that the physical structure of distinct scaffolds induces unique signaling cascades that regulate migration and morphology in embryonic neural precursor cells. J. Comp. Neurol. 524:3485-3502, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Pathology, Division of Neuropathology, The Ohio State University College of Medicine, Columbus, Ohio, 43210.
authors.forename: Catherine
authors.initials: C
authors.lastname: Czeisler
authors.affiliation: Department of Biomedical Engineering, The Ohio State University College of Engineering, Columbus, Ohio, 43210.
authors.forename: Aaron
authors.initials: A
authors.lastname: Short
authors.affiliation: Department of Biomedical Engineering, The Ohio State University College of Engineering, Columbus, Ohio, 43210.
authors.forename: Tyler
authors.initials: T
authors.lastname: Nelson
authors.affiliation: Department of Pathology, Division of Neuropathology, The Ohio State University College of Medicine, Columbus, Ohio, 43210.
authors.forename: Patrick
authors.initials: P
authors.lastname: Gygli
authors.affiliation: Department of Pathology, Division of Neuropathology, The Ohio State University College of Medicine, Columbus, Ohio, 43210.
authors.forename: Cristina
authors.initials: C
authors.lastname: Ortiz
authors.affiliation: Department of Pathology, Division of Neuropathology, The Ohio State University College of Medicine, Columbus, Ohio, 43210.
authors.forename: Fay Patsy
authors.initials: FP
authors.lastname: Catacutan
authors.affiliation: Department of Pathology, Division of Neuropathology, The Ohio State University College of Medicine, Columbus, Ohio, 43210.
authors.forename: Ben
authors.initials: B
authors.lastname: Stocker
authors.affiliation: Department of Pathology, Division of Neuropathology, The Ohio State University College of Medicine, Columbus, Ohio, 43210.
authors.forename: James
authors.initials: J
authors.lastname: Cronin
authors.affiliation: Department of Materials Science and Engineering, the Ohio State University College of Engineering, Columbus, Ohio, 43210.
authors.forename: John
authors.initials: J
authors.lastname: Lannutti
authors.affiliation: Department of Biomedical Engineering, The Ohio State University College of Engineering, Columbus, Ohio, 43210. jose.otero@osumc.edu.|William G. Lowrie Department of Chemical Engineering, The Ohio State University College of Engineering, Columbus, Ohio, 43210. jose.otero@osumc.edu.
authors.forename: Jessica
authors.initials: J
authors.lastname: Winter
authors.affiliation: Department of Pathology, Division of Neuropathology, The Ohio State University College of Medicine, Columbus, Ohio, 43210. winter.63@osu.edu.
authors.forename: José Javier
authors.initials: JJ
authors.lastname: Otero
mesh_terms: D000199:Actins / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D007797:Laminin / Q000378:metabolism; D008297:Male; D051379:Mice; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D008959:Models, Neurological; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D011091:Polyesters; D013499:Surface Properties; D054457:Tissue Scaffolds; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000199:Actins; D007797:Laminin; D011091:Polyesters; C016240:polycaprolactone; D054460:rho-Associated Kinases
keywords: RRID: AB_2313773; RRID: AB_305808; RRID: AB_477010; RRID: AB_531887; RRID: AB_561007; RRID: AB_628431; RRID: SCR_001905; RRID: SCR_002285; RRID: SCR_013672; RRID: SCR_014242; RRID: SciRes_000136; actin; cytoskeleton; laminin; microtubules; migration; neural stem cell; topography