The transcription factor BCL11A defines distinct subsets of midbrain dopaminergic neurons
Summary: Midbrain dopaminergic (mDA) neurons are diverse in their projection targets, effect on behavior, and susceptibility to neurodegeneration. Little is known about the molecular mechanisms establishing this diversity during development. We show that the transcription factor BCL11A is expressed...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-09-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S221112472101144X |
| _version_ | 1819123405380648960 |
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| author | Marianna Tolve Ayse Ulusoy Nikolaos Patikas K. Ushna S. Islam Gabriela O. Bodea Ece Öztürk Bianca Broske Astrid Mentani Antonia Wagener Karen M.J. van Loo Stefan Britsch Pengtao Liu Walid T. Khaled Emmanouil Metzakopian Stephan L. Baader Donato A. Di Monte Sandra Blaess |
| author_facet | Marianna Tolve Ayse Ulusoy Nikolaos Patikas K. Ushna S. Islam Gabriela O. Bodea Ece Öztürk Bianca Broske Astrid Mentani Antonia Wagener Karen M.J. van Loo Stefan Britsch Pengtao Liu Walid T. Khaled Emmanouil Metzakopian Stephan L. Baader Donato A. Di Monte Sandra Blaess |
| author_sort | Marianna Tolve |
| collection | DOAJ |
| description | Summary: Midbrain dopaminergic (mDA) neurons are diverse in their projection targets, effect on behavior, and susceptibility to neurodegeneration. Little is known about the molecular mechanisms establishing this diversity during development. We show that the transcription factor BCL11A is expressed in a subset of mDA neurons in the developing and adult murine brain and in a subpopulation of pluripotent-stem-cell-derived human mDA neurons. By combining intersectional labeling and viral-mediated tracing, we demonstrate that Bcl11a-expressing mDA neurons form a highly specific subcircuit within the murine dopaminergic system. In the substantia nigra, the Bcl11a-expressing mDA subset is particularly vulnerable to neurodegeneration upon α-synuclein overexpression or oxidative stress. Inactivation of Bcl11a in murine mDA neurons increases this susceptibility further, alters the distribution of mDA neurons, and results in deficits in skilled motor behavior. In summary, BCL11A defines mDA subpopulations with highly distinctive characteristics and is required for establishing and maintaining their normal physiology. |
| first_indexed | 2024-12-22T07:07:50Z |
| format | Article |
| id | doaj.art-84e84243de1b429cb15f926080222297 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-22T07:07:50Z |
| publishDate | 2021-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-84e84243de1b429cb15f9260802222972022-12-21T18:34:37ZengElsevierCell Reports2211-12472021-09-013611109697The transcription factor BCL11A defines distinct subsets of midbrain dopaminergic neuronsMarianna Tolve0Ayse Ulusoy1Nikolaos Patikas2K. Ushna S. Islam3Gabriela O. Bodea4Ece Öztürk5Bianca Broske6Astrid Mentani7Antonia Wagener8Karen M.J. van Loo9Stefan Britsch10Pengtao Liu11Walid T. Khaled12Emmanouil Metzakopian13Stephan L. Baader14Donato A. Di Monte15Sandra Blaess16Neurodevelopmental Genetics, Institute of Reconstructive Neurobiology, Medical Faculty, University of Bonn, 53127 Bonn, GermanyGerman Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, GermanyUK Dementia Research Institute, Department of Clinical Neurosciences, Cambridge Biomedical Campus, University of Cambridge, Cambridge, CB2 0AH, UKNeurodevelopmental Genetics, Institute of Reconstructive Neurobiology, Medical Faculty, University of Bonn, 53127 Bonn, GermanyNeurodevelopmental Genetics, Institute of Reconstructive Neurobiology, Medical Faculty, University of Bonn, 53127 Bonn, GermanyNeurodevelopmental Genetics, Institute of Reconstructive Neurobiology, Medical Faculty, University of Bonn, 53127 Bonn, GermanyNeurodevelopmental Genetics, Institute of Reconstructive Neurobiology, Medical Faculty, University of Bonn, 53127 Bonn, GermanyNeurodevelopmental Genetics, Institute of Reconstructive Neurobiology, Medical Faculty, University of Bonn, 53127 Bonn, GermanyNeurodevelopmental Genetics, Institute of Reconstructive Neurobiology, Medical Faculty, University of Bonn, 53127 Bonn, GermanySection for Translational Epilepsy Research, Department of Neuropathology, Medical Faculty, University of Bonn, 53127 Bonn, GermanyInstitute of Molecular and Cellular Anatomy, Ulm University, 89081 Ulm, GermanySchool of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, ChinaDepartment of Pharmacology, University of Cambridge, Cambridge, CB 21PD, UK; Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, CB2 0AW, UKUK Dementia Research Institute, Department of Clinical Neurosciences, Cambridge Biomedical Campus, University of Cambridge, Cambridge, CB2 0AH, UKInstitute of Anatomy, Anatomy and Cell Biology, Medical Faculty, University of Bonn, 53115 Bonn, GermanyGerman Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, GermanyNeurodevelopmental Genetics, Institute of Reconstructive Neurobiology, Medical Faculty, University of Bonn, 53127 Bonn, Germany; Corresponding authorSummary: Midbrain dopaminergic (mDA) neurons are diverse in their projection targets, effect on behavior, and susceptibility to neurodegeneration. Little is known about the molecular mechanisms establishing this diversity during development. We show that the transcription factor BCL11A is expressed in a subset of mDA neurons in the developing and adult murine brain and in a subpopulation of pluripotent-stem-cell-derived human mDA neurons. By combining intersectional labeling and viral-mediated tracing, we demonstrate that Bcl11a-expressing mDA neurons form a highly specific subcircuit within the murine dopaminergic system. In the substantia nigra, the Bcl11a-expressing mDA subset is particularly vulnerable to neurodegeneration upon α-synuclein overexpression or oxidative stress. Inactivation of Bcl11a in murine mDA neurons increases this susceptibility further, alters the distribution of mDA neurons, and results in deficits in skilled motor behavior. In summary, BCL11A defines mDA subpopulations with highly distinctive characteristics and is required for establishing and maintaining their normal physiology.http://www.sciencedirect.com/science/article/pii/S221112472101144Xdopaminergic neuronsdevelopmentneuronal diversitycircuitsbehaviortranscription factor |
| spellingShingle | Marianna Tolve Ayse Ulusoy Nikolaos Patikas K. Ushna S. Islam Gabriela O. Bodea Ece Öztürk Bianca Broske Astrid Mentani Antonia Wagener Karen M.J. van Loo Stefan Britsch Pengtao Liu Walid T. Khaled Emmanouil Metzakopian Stephan L. Baader Donato A. Di Monte Sandra Blaess The transcription factor BCL11A defines distinct subsets of midbrain dopaminergic neurons Cell Reports dopaminergic neurons development neuronal diversity circuits behavior transcription factor |
| title | The transcription factor BCL11A defines distinct subsets of midbrain dopaminergic neurons |
| title_full | The transcription factor BCL11A defines distinct subsets of midbrain dopaminergic neurons |
| title_fullStr | The transcription factor BCL11A defines distinct subsets of midbrain dopaminergic neurons |
| title_full_unstemmed | The transcription factor BCL11A defines distinct subsets of midbrain dopaminergic neurons |
| title_short | The transcription factor BCL11A defines distinct subsets of midbrain dopaminergic neurons |
| title_sort | transcription factor bcl11a defines distinct subsets of midbrain dopaminergic neurons |
| topic | dopaminergic neurons development neuronal diversity circuits behavior transcription factor |
| url | http://www.sciencedirect.com/science/article/pii/S221112472101144X |
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