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Transcriptional repression of Plxnc1 by Lmx1a and Lmx1b directs topographic dopaminergic circuit formation
Mesodiencephalic dopamine neurons play central roles in the regulation of a wide range of brain functions, including voluntary movement and behavioral processes. These functions are served by distinct subtypes of mesodiencephalic dopamine neurons located in the substantia nigra pars compacta and the...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5643336/ https://www.ncbi.nlm.nih.gov/pubmed/29038581 http://dx.doi.org/10.1038/s41467-017-01042-0 |
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author | Chabrat, Audrey Brisson, Guillaume Doucet-Beaupré, Hélène Salesse, Charleen Schaan Profes, Marcos Dovonou, Axelle Akitegetse, Cléophace Charest, Julien Lemstra, Suzanne Côté, Daniel Pasterkamp, R. Jeroen Abrudan, Monica I. Metzakopian, Emmanouil Ang, Siew-Lan Lévesque, Martin |
author_facet | Chabrat, Audrey Brisson, Guillaume Doucet-Beaupré, Hélène Salesse, Charleen Schaan Profes, Marcos Dovonou, Axelle Akitegetse, Cléophace Charest, Julien Lemstra, Suzanne Côté, Daniel Pasterkamp, R. Jeroen Abrudan, Monica I. Metzakopian, Emmanouil Ang, Siew-Lan Lévesque, Martin |
author_sort | Chabrat, Audrey |
collection | PubMed |
description | Mesodiencephalic dopamine neurons play central roles in the regulation of a wide range of brain functions, including voluntary movement and behavioral processes. These functions are served by distinct subtypes of mesodiencephalic dopamine neurons located in the substantia nigra pars compacta and the ventral tegmental area, which form the nigrostriatal, mesolimbic, and mesocortical pathways. Until now, mechanisms involved in dopaminergic circuit formation remained largely unknown. Here, we show that Lmx1a, Lmx1b, and Otx2 transcription factors control subtype-specific mesodiencephalic dopamine neurons and their appropriate axon innervation. Our results revealed that the expression of Plxnc1, an axon guidance receptor, is repressed by Lmx1a/b and enhanced by Otx2. We also found that Sema7a/Plxnc1 interactions are responsible for the segregation of nigrostriatal and mesolimbic dopaminergic pathways. These findings identify Lmx1a/b, Otx2, and Plxnc1 as determinants of dopaminergic circuit formation and should assist in engineering mesodiencephalic dopamine neurons capable of regenerating appropriate connections for cell therapy. |
format | Online Article Text |
id | pubmed-5643336 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-56433362017-10-18 Transcriptional repression of Plxnc1 by Lmx1a and Lmx1b directs topographic dopaminergic circuit formation Chabrat, Audrey Brisson, Guillaume Doucet-Beaupré, Hélène Salesse, Charleen Schaan Profes, Marcos Dovonou, Axelle Akitegetse, Cléophace Charest, Julien Lemstra, Suzanne Côté, Daniel Pasterkamp, R. Jeroen Abrudan, Monica I. Metzakopian, Emmanouil Ang, Siew-Lan Lévesque, Martin Nat Commun Article Mesodiencephalic dopamine neurons play central roles in the regulation of a wide range of brain functions, including voluntary movement and behavioral processes. These functions are served by distinct subtypes of mesodiencephalic dopamine neurons located in the substantia nigra pars compacta and the ventral tegmental area, which form the nigrostriatal, mesolimbic, and mesocortical pathways. Until now, mechanisms involved in dopaminergic circuit formation remained largely unknown. Here, we show that Lmx1a, Lmx1b, and Otx2 transcription factors control subtype-specific mesodiencephalic dopamine neurons and their appropriate axon innervation. Our results revealed that the expression of Plxnc1, an axon guidance receptor, is repressed by Lmx1a/b and enhanced by Otx2. We also found that Sema7a/Plxnc1 interactions are responsible for the segregation of nigrostriatal and mesolimbic dopaminergic pathways. These findings identify Lmx1a/b, Otx2, and Plxnc1 as determinants of dopaminergic circuit formation and should assist in engineering mesodiencephalic dopamine neurons capable of regenerating appropriate connections for cell therapy. Nature Publishing Group UK 2017-10-16 /pmc/articles/PMC5643336/ /pubmed/29038581 http://dx.doi.org/10.1038/s41467-017-01042-0 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Chabrat, Audrey Brisson, Guillaume Doucet-Beaupré, Hélène Salesse, Charleen Schaan Profes, Marcos Dovonou, Axelle Akitegetse, Cléophace Charest, Julien Lemstra, Suzanne Côté, Daniel Pasterkamp, R. Jeroen Abrudan, Monica I. Metzakopian, Emmanouil Ang, Siew-Lan Lévesque, Martin Transcriptional repression of Plxnc1 by Lmx1a and Lmx1b directs topographic dopaminergic circuit formation |
title | Transcriptional repression of Plxnc1 by Lmx1a and Lmx1b directs topographic dopaminergic circuit formation |
title_full | Transcriptional repression of Plxnc1 by Lmx1a and Lmx1b directs topographic dopaminergic circuit formation |
title_fullStr | Transcriptional repression of Plxnc1 by Lmx1a and Lmx1b directs topographic dopaminergic circuit formation |
title_full_unstemmed | Transcriptional repression of Plxnc1 by Lmx1a and Lmx1b directs topographic dopaminergic circuit formation |
title_short | Transcriptional repression of Plxnc1 by Lmx1a and Lmx1b directs topographic dopaminergic circuit formation |
title_sort | transcriptional repression of plxnc1 by lmx1a and lmx1b directs topographic dopaminergic circuit formation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5643336/ https://www.ncbi.nlm.nih.gov/pubmed/29038581 http://dx.doi.org/10.1038/s41467-017-01042-0 |
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