The transcription factor BCL11A defines distinct subsets of midbrain dopaminergic neurons.

Autor:	Tolve M; Neurodevelopmental Genetics, Institute of Reconstructive Neurobiology, Medical Faculty, University of Bonn, 53127 Bonn, Germany., Ulusoy A; German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany., Patikas N; UK Dementia Research Institute, Department of Clinical Neurosciences, Cambridge Biomedical Campus, University of Cambridge, Cambridge, CB2 0AH, UK., Islam KUS; Neurodevelopmental Genetics, Institute of Reconstructive Neurobiology, Medical Faculty, University of Bonn, 53127 Bonn, Germany., Bodea GO; Neurodevelopmental Genetics, Institute of Reconstructive Neurobiology, Medical Faculty, University of Bonn, 53127 Bonn, Germany., Öztürk E; Neurodevelopmental Genetics, Institute of Reconstructive Neurobiology, Medical Faculty, University of Bonn, 53127 Bonn, Germany., Broske B; Neurodevelopmental Genetics, Institute of Reconstructive Neurobiology, Medical Faculty, University of Bonn, 53127 Bonn, Germany., Mentani A; Neurodevelopmental Genetics, Institute of Reconstructive Neurobiology, Medical Faculty, University of Bonn, 53127 Bonn, Germany., Wagener A; Neurodevelopmental Genetics, Institute of Reconstructive Neurobiology, Medical Faculty, University of Bonn, 53127 Bonn, Germany., van Loo KMJ; Section for Translational Epilepsy Research, Department of Neuropathology, Medical Faculty, University of Bonn, 53127 Bonn, Germany., Britsch S; Institute of Molecular and Cellular Anatomy, Ulm University, 89081 Ulm, Germany., Liu P; School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China., Khaled WT; Department of Pharmacology, University of Cambridge, Cambridge, CB 21PD, UK; Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, CB2 0AW, UK., Metzakopian E; UK Dementia Research Institute, Department of Clinical Neurosciences, Cambridge Biomedical Campus, University of Cambridge, Cambridge, CB2 0AH, UK., Baader SL; Institute of Anatomy, Anatomy and Cell Biology, Medical Faculty, University of Bonn, 53115 Bonn, Germany., Di Monte DA; German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany., Blaess S; Neurodevelopmental Genetics, Institute of Reconstructive Neurobiology, Medical Faculty, University of Bonn, 53127 Bonn, Germany. Electronic address: sblaess@uni-bonn.de.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2021 Sep 14; Vol. 36 (11), pp. 109697.
DOI:	10.1016/j.celrep.2021.109697
Abstrakt:	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. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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