24 research outputs found

    Bioelectricity Buzz

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    Requirement of Pax6 for the integration of guidance cues in cell migration

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    Data accessibility. Cell trajectories data and a summary of directedness and angle values are deposited at Dryad: http://dx.doi.org/10.5061/dryad.53512. Funding MA was funded by an Alban International Research Studentship (code: E07D400602UY).Peer reviewedPublisher PD

    Contact-mediated control of radial migration of corneal epithelial cells

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    We thank Darrin Sheppard and other staff at the University of Aberdeen Medical Research Facility for specialist technical assistance. We thank Patsy D. Goast for overnight microscope monitoring. This work was performed under the Biotechnology and Bioscience Research Council Grant number BB/E015840/1 to JMC.Peer reviewedPublisher PD

    Electric field gradients and bipolar electrochemistry effects on neural growth : A finite element study on immersed electroactive conducting electrode materials

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    Acknowledgments This work was funded by the European Commission FP6 NEST Program (Contract 028473), RTI2018-097753, MAT2011-24363 and MAT2015-65192-R from the Spanish Science Ministry, La Marató de TV3 Foundation (Identification Number 110131), and Severo Ochoa Programme for Centres of Excellence in R&D (SEV-2015-0496). LI. Abad thanks MINECO for a Ramón y Cajal Contract (RYC-2013-12640). The authors also thank A. Beardo (NanoTransport group from UAB) for useful discussions.Peer reviewedPostprin

    The Direction of Neurite Growth in a Weak DC Electric Field Depends on the Substratum: Contributions of Adhesivity and Net Surface Charge

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    AbstractWe investigated the influence of the growth surface on the direction ofXenopusspinal neurite growth in the presence of a dc electric field of physiological magnitude. The direction of galvanotropism was determined by the substratum; neurites grew toward the negative electrode (cathode) on untreated Falcon tissue culture plastic or on laminin substrata, which are negatively charged, but neurites growing on polylysine, which is positively charged, turned toward the positive electrode (anode). Growth was oriented randomly on all substrata without an electric field. We tested the hypothesis that the charge of the growth surface was responsible for reversed galvanotropism on polylysine by growing neurons on tissue culture dishes with different net surface charges. Although neurites grew cathodally on both Plastek substrata, the frequency of anodal turning was greater on dishes with a net positive charge (Plastek C) than on those with a net negative charge (Plastek M). The charge of the growth surface therefore influenced the frequency of anodal galvanotropism but a reversal in surface charge was insufficient to reverse galvanotropism completely, possibly because of differences in the relative magnitude of the substratum charge densities. The influence of substratum adhesion on galvanotropism was considered by growing neurites on a range of polylysine concentrations. Growth cone to substratum adhesivity was measured using a blasting assay. Adhesivity and the frequency of anodal turning were graded over the range of polylysine concentrations (0 = 0.1 < 1 < 10 = 100 μg/ml). The direction of neurite growth in an electric field is therefore influenced by both substratum charge and growth cone-to-substratum adhesivity. These data are consistent with the idea that spatial or temporal variation in the expression of adhesion molecules in embryos may interact with naturally occurring electric fields to enhance growth cone pathfinding

    The core planar cell polarity gene, Vangl2, directs adult corneal epithelial cell alignment and migration

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    This work was supported by a Biotechnology and Biological Sciences Research Council (BBSRC) DTG PhD studentship to A.F., an Anatomical Society PhD Studentship (‘The Roles of planar cell polarity genes in a classical anatomical system: the cornea’) to D.A.P./J.M.C. and BBSRC Project Grants BB/J015172/1 and BB/J015237/1 to J.D.W. and J.M.C., respectively.Peer reviewedPublisher PD

    Physiological strength electric fields modulate human T cell activation and polarisation

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    Acknowledgements: This work was supported by grants from an NHS Grampian Endowment Fund (Grant number 10/19). C.E.A was supported by an Institution of Medical Science University studentship. The authors acknowledge and are grateful to all volunteers for donating blood for T cell isolation. The authors also thank the University of Aberdeen Iain Fraser Cytometry Centre for their assistance.Peer reviewedPublisher PD

    Interaction between hedgehog signalling and PAX6 dosage mediates maintenance and regeneration of the corneal epithelium

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    PURPOSE: To investigate the roles of intracellular signaling elicited by Hedgehog (Hh) ligands in corneal maintenance and wound healing. METHODS: The expression of Hedgehog pathway components in the cornea was assayed by immunohistochemistry, western blot and reverse-transcription polymerase chain reaction (RT-PCR), in wild-type mice and mice that were heterozygous null for the gene encoding the transcription factor, paired box gene 6 (Pax6). Corneal epithelial wound healing and cell migration assays were performed after pharmacological upregulation and downregulation of the hedgehog pathway. Reporter mice, mosaic for expression of the gene encoding β-galactosidase (LacZ), were crossed to Pax6(+/-) mice, mice heterozygous for the gene encoding GLI-Kruppel family member GLI3, and Pax6(+/-)Gli3(+/-) double heterozygotes, to assay patterns of cell migration and corneal epithelial organization in vivo. RESULTS: Corneal epithelial wound healing rates increased in response to application of Sonic hedgehog (Shh), but only in mice with wild-type Pax6 dosage. Downregulation of Hedgehog signalling inhibited corneal epithelial cell proliferation. Pax6(+/-) corneal epithelia showed increased proliferation in response to exogenous Shh, but not increased migration. Desert hedgehog (Dhh) was shown to be the major endogenous ligand, with Shh detectable only by RT-PCR and only after epithelial wounding. The activity of phosphatidylinositol-3-OH kinase-γ (PI3Kγ) was not required for the increased migration response in response to Shh. Nuclear expression of the activator form of the transcription factor Gli3 (which mediates Hh signalling) was reduced in Pax6(+/-) corneal epithelia. Pax6(+/-)Gli3(+/-) double heterozygotes showed highly disrupted patterns of clonal arrangement of cells in the corneal epithelium. CONCLUSIONS: The data show key roles for endogenous Dhh signalling in maintenance and regeneration of the corneal epithelium, demonstrate an interaction between Pax6 and Hh signalling in the corneal epithelium, and show that failure of Hh signalling pathways is a feature of Pax6(+/-) corneal disease that cannot be remedied pharmacologically by addition of the ligands

    Roles for IFT172 and primary cilia in cell migration, cell division and neocortex development

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    This work is supported by the grants from National Natural Science Foundation of China (31528011, B.L.; 81571332, 91232724, Y.D.), Key Research and Development Program from Hunan Province (2018DK2011), Shanghai Municipal Science and Technology Major Project (2018SHZDZX01) and ZJLab. We are grateful to Prof. Tamara Caspary for providing the WIM and WT cells. M.P. was funded by a Scottish Universities Life Sciences Alliance (SULSA) studentship to C.M. and a Scholarship from Chinese Scholarship Council (CSC). L. H. is also a Scholarship awardee of CSC.Peer reviewedPublisher PD
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