Home > Publications Database > The transcription factor BCL11A defines distinct subsets of midbrain dopaminergic neurons. > print

001     162865
005     20230915092411.0
024 7 _ |a 10.1016/j.celrep.2021.109697
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024 7 _ |a 2211-1247
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024 7 _ |a 2639-1856
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037 _ _ |a DZNE-2021-01520
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Tolve, Marianna
|b 0
245 _ _ |a The transcription factor BCL11A defines distinct subsets of midbrain dopaminergic neurons.
260 _ _ |a [New York, NY]
|c 2021
|b Elsevier
336 7 _ |a article
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336 7 _ |a Journal Article
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500 _ _ |a CC BY-NC-ND
520 _ _ |a 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.
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650 _ 7 |a alpha-synuclein
|2 Other
650 _ 7 |a behavior
|2 Other
650 _ 7 |a circuits
|2 Other
650 _ 7 |a development
|2 Other
650 _ 7 |a dopaminergic neurons
|2 Other
650 _ 7 |a iPSCs
|2 Other
650 _ 7 |a mouse
|2 Other
650 _ 7 |a neurodegeneration
|2 Other
650 _ 7 |a neuronal diversity
|2 Other
650 _ 7 |a transcription factor
|2 Other
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Behavior, Animal
|2 MeSH
650 _ 2 |a Brain: metabolism
|2 MeSH
650 _ 2 |a Dopamine: metabolism
|2 MeSH
650 _ 2 |a Dopaminergic Neurons: metabolism
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Induced Pluripotent Stem Cells: cytology
|2 MeSH
650 _ 2 |a Induced Pluripotent Stem Cells: metabolism
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Mice, Knockout
|2 MeSH
650 _ 2 |a Repressor Proteins: deficiency
|2 MeSH
650 _ 2 |a Repressor Proteins: genetics
|2 MeSH
650 _ 2 |a Repressor Proteins: metabolism
|2 MeSH
650 _ 2 |a Substantia Nigra: metabolism
|2 MeSH
650 _ 2 |a Substantia Nigra: pathology
|2 MeSH
650 _ 2 |a Transcriptome
|2 MeSH
650 _ 2 |a Ventral Tegmental Area: metabolism
|2 MeSH
650 _ 2 |a Ventral Tegmental Area: pathology
|2 MeSH
650 _ 2 |a alpha-Synuclein: genetics
|2 MeSH
650 _ 2 |a alpha-Synuclein: metabolism
|2 MeSH
700 1 _ |a Ulusoy, Ayse
|0 P:(DE-2719)2772760
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700 1 _ |a Patikas, Nikolaos
|b 2
700 1 _ |a Islam, K Ushna S
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700 1 _ |a Bodea, Gabriela O
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700 1 _ |a Öztürk, Ece
|b 5
700 1 _ |a Broske, Bianca
|b 6
700 1 _ |a Mentani, Astrid
|b 7
700 1 _ |a Wagener, Antonia
|b 8
700 1 _ |a van Loo, Karen M J
|b 9
700 1 _ |a Britsch, Stefan
|b 10
700 1 _ |a Liu, Pengtao
|b 11
700 1 _ |a Khaled, Walid T
|b 12
700 1 _ |a Metzakopian, Emmanouil
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700 1 _ |a Baader, Stephan L
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700 1 _ |a Di Monte, Donato A
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700 1 _ |a Blaess, Sandra
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773 _ _ |a 10.1016/j.celrep.2021.109697
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