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000162865 037__ $$aDZNE-2021-01520
000162865 041__ $$aEnglish
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000162865 1001_ $$aTolve, Marianna$$b0
000162865 245__ $$aThe transcription factor BCL11A defines distinct subsets of midbrain dopaminergic neurons.
000162865 260__ $$a[New York, NY]$$bElsevier$$c2021
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000162865 520__ $$aMidbrain dopaminergic (mDA) neurons are diverse in their projection targets, effect on behavior, and susceptibility to neurodegeneration. Little is known about the molecular mechanisms establishing this diversity during development. We show that the transcription factor BCL11A is expressed in a subset of mDA neurons in the developing and adult murine brain and in a subpopulation of pluripotent-stem-cell-derived human mDA neurons. By combining intersectional labeling and viral-mediated tracing, we demonstrate that Bcl11a-expressing mDA neurons form a highly specific subcircuit within the murine dopaminergic system. In the substantia nigra, the Bcl11a-expressing mDA subset is particularly vulnerable to neurodegeneration upon α-synuclein overexpression or oxidative stress. Inactivation of Bcl11a in murine mDA neurons increases this susceptibility further, alters the distribution of mDA neurons, and results in deficits in skilled motor behavior. In summary, BCL11A defines mDA subpopulations with highly distinctive characteristics and is required for establishing and maintaining their normal physiology.
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000162865 650_7 $$2Other$$aalpha-synuclein
000162865 650_7 $$2Other$$abehavior
000162865 650_7 $$2Other$$acircuits
000162865 650_7 $$2Other$$adevelopment
000162865 650_7 $$2Other$$adopaminergic neurons
000162865 650_7 $$2Other$$aiPSCs
000162865 650_7 $$2Other$$amouse
000162865 650_7 $$2Other$$aneurodegeneration
000162865 650_7 $$2Other$$aneuronal diversity
000162865 650_7 $$2Other$$atranscription factor
000162865 650_2 $$2MeSH$$aAnimals
000162865 650_2 $$2MeSH$$aBehavior, Animal
000162865 650_2 $$2MeSH$$aBrain: metabolism
000162865 650_2 $$2MeSH$$aDopamine: metabolism
000162865 650_2 $$2MeSH$$aDopaminergic Neurons: metabolism
000162865 650_2 $$2MeSH$$aHumans
000162865 650_2 $$2MeSH$$aInduced Pluripotent Stem Cells: cytology
000162865 650_2 $$2MeSH$$aInduced Pluripotent Stem Cells: metabolism
000162865 650_2 $$2MeSH$$aMale
000162865 650_2 $$2MeSH$$aMice
000162865 650_2 $$2MeSH$$aMice, Knockout
000162865 650_2 $$2MeSH$$aRepressor Proteins: deficiency
000162865 650_2 $$2MeSH$$aRepressor Proteins: genetics
000162865 650_2 $$2MeSH$$aRepressor Proteins: metabolism
000162865 650_2 $$2MeSH$$aSubstantia Nigra: metabolism
000162865 650_2 $$2MeSH$$aSubstantia Nigra: pathology
000162865 650_2 $$2MeSH$$aTranscriptome
000162865 650_2 $$2MeSH$$aVentral Tegmental Area: metabolism
000162865 650_2 $$2MeSH$$aVentral Tegmental Area: pathology
000162865 650_2 $$2MeSH$$aalpha-Synuclein: genetics
000162865 650_2 $$2MeSH$$aalpha-Synuclein: metabolism
000162865 7001_ $$0P:(DE-2719)2772760$$aUlusoy, Ayse$$b1$$udzne
000162865 7001_ $$aPatikas, Nikolaos$$b2
000162865 7001_ $$aIslam, K Ushna S$$b3
000162865 7001_ $$aBodea, Gabriela O$$b4
000162865 7001_ $$aÖztürk, Ece$$b5
000162865 7001_ $$aBroske, Bianca$$b6
000162865 7001_ $$aMentani, Astrid$$b7
000162865 7001_ $$aWagener, Antonia$$b8
000162865 7001_ $$avan Loo, Karen M J$$b9
000162865 7001_ $$aBritsch, Stefan$$b10
000162865 7001_ $$aLiu, Pengtao$$b11
000162865 7001_ $$aKhaled, Walid T$$b12
000162865 7001_ $$aMetzakopian, Emmanouil$$b13
000162865 7001_ $$aBaader, Stephan L$$b14
000162865 7001_ $$0P:(DE-2719)2481741$$aDi Monte, Donato A$$b15$$udzne
000162865 7001_ $$aBlaess, Sandra$$b16
000162865 773__ $$0PERI:(DE-600)2649101-1$$a10.1016/j.celrep.2021.109697$$gVol. 36, no. 11, p. 109697 -$$n11$$p109697$$tCell reports$$v36$$x2211-1247$$y2021
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