Zeb2 is a negative regulator of midbrain dopaminergic axon growth and target innervation

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dc.contributor.author Hegarty, Shane V.
dc.contributor.author Wyatt, Sean L.
dc.contributor.author Howard, Laura
dc.contributor.author Stappers, Elke
dc.contributor.author Huylebroeck, Danny
dc.contributor.author Sullivan, Aideen M.
dc.contributor.author O'Keeffe, Gerard W.
dc.date.accessioned 2017-09-26T11:39:23Z
dc.date.available 2017-09-26T11:39:23Z
dc.date.issued 2017
dc.identifier.citation Hegarty, S. V., Wyatt, S. L., Howard, L., Stappers, E., Huylebroeck, D., Sullivan, A. M. and O’Keeffe, G. W. (2017) 'Zeb2 is a negative regulator of midbrain dopaminergic axon growth and target innervation', Scientific Reports, 7(1), 8568 (11pp). doi: 10.1038/s41598-017-08900-3 en
dc.identifier.volume 7
dc.identifier.issn 2045-2322
dc.identifier.uri http://hdl.handle.net/10468/4805
dc.identifier.doi 10.1038/s41598-017-08900-3
dc.description.abstract Neural connectivity requires neuronal differentiation, axon growth, and precise target innervation. Midbrain dopaminergic neurons project via the nigrostriatal pathway to the striatum to regulate voluntary movement. While the specification and differentiation of these neurons have been extensively studied, the molecular mechanisms that regulate midbrain dopaminergic axon growth and target innervation are less clear. Here we show that the transcription factor Zeb2 cell-autonomously represses Smad signalling to limit midbrain dopaminergic axon growth and target innervation. Zeb2 levels are downregulated in the embryonic rodent midbrain during the period of dopaminergic axon growth, when BMP pathway components are upregulated. Experimental knockdown of Zeb2 leads to an increase in BMP-Smad-dependent axon growth. Consequently there is dopaminergic hyperinnervation of the striatum, without an increase in the numbers of midbrain dopaminergic neurons, in conditional Zeb2 (Nestin-Cre based) knockout mice. Therefore, these findings reveal a new mechanism for the regulation of midbrain dopaminergic axon growth during central nervous system development. en
dc.description.sponsorship Fonds Wetenschappelijk Onderzoek (FWO-VG.0782.14); Federaal Wetenschapsbeleid (Belspo) (IAP7-07 DevRepair) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Nature Publishing Group en
dc.relation.uri https://www.nature.com/articles/s41598-017-08900-3
dc.rights © 2017, the Authors. Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. en
dc.rights.uri https://creativecommons.org/licenses/by/4.0/
dc.subject Neurons in vitro en
dc.subject Schwann cell differentiation en
dc.subject Nervous system development en
dc.subject Parkinsons disease en
dc.subject Neurite growth en
dc.subject Factor beta en
dc.subject Sip1 en
dc.subject Morphology en
dc.subject Repressor en
dc.subject Survival en
dc.title Zeb2 is a negative regulator of midbrain dopaminergic axon growth and target innervation en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Aideen Sullivan, Anatomy & Neuroscience, University College Cork, Cork, Ireland. +353-21-490-3000 Email: a.sullivan@ucc.ie en
dc.internal.availability Full text available en
dc.description.version Published Version en
dc.internal.wokid WOS:000407864000035
dc.contributor.funder Irish Research Council
dc.contributor.funder Royal Irish Academy
dc.contributor.funder Science Foundation Ireland
dc.contributor.funder Fonds Wetenschappelijk Onderzoek
dc.contributor.funder Federaal Wetenschapsbeleid
dc.contributor.funder Erasmus Medisch Centrum
dc.description.status Peer reviewed en
dc.identifier.journaltitle Scientific Reports en
dc.internal.IRISemailaddress a.sullivan@ucc.ie en
dc.identifier.articleid 8568
dc.relation.project info:eu-repo/grantAgreement/SFI/SFI Career Development Award/15/CDA/3498/IE/Development of GDF5 neurotrophic factor therapy for Parkinson_s disease./
dc.relation.project info:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2272/IE/Irish Centre for Fetal and Neonatal Translational Research (INFANT)/


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© 2017, the Authors. Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Except where otherwise noted, this item's license is described as © 2017, the Authors. Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
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