TY  - JOUR
AU  - Tolve, Marianna
AU  - Ulusoy, Ayse
AU  - Patikas, Nikolaos
AU  - Islam, K Ushna S
AU  - Bodea, Gabriela O
AU  - Öztürk, Ece
AU  - Broske, Bianca
AU  - Mentani, Astrid
AU  - Wagener, Antonia
AU  - van Loo, Karen M J
AU  - Britsch, Stefan
AU  - Liu, Pengtao
AU  - Khaled, Walid T
AU  - Metzakopian, Emmanouil
AU  - Baader, Stephan L
AU  - Di Monte, Donato A
AU  - Blaess, Sandra
TI  - The transcription factor BCL11A defines distinct subsets of midbrain dopaminergic neurons.
JO  - Cell reports
VL  - 36
IS  - 11
SN  - 2211-1247
CY  - [New York, NY]
PB  - Elsevier
M1  - DZNE-2021-01520
SP  - 109697
PY  - 2021
N1  - CC BY-NC-ND
AB  - 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.
KW  - Animals
KW  - Behavior, Animal
KW  - Brain: metabolism
KW  - Dopamine: metabolism
KW  - Dopaminergic Neurons: metabolism
KW  - Humans
KW  - Induced Pluripotent Stem Cells: cytology
KW  - Induced Pluripotent Stem Cells: metabolism
KW  - Male
KW  - Mice
KW  - Mice, Knockout
KW  - Repressor Proteins: deficiency
KW  - Repressor Proteins: genetics
KW  - Repressor Proteins: metabolism
KW  - Substantia Nigra: metabolism
KW  - Substantia Nigra: pathology
KW  - Transcriptome
KW  - Ventral Tegmental Area: metabolism
KW  - Ventral Tegmental Area: pathology
KW  - alpha-Synuclein: genetics
KW  - alpha-Synuclein: metabolism
KW  - alpha-synuclein (Other)
KW  - behavior (Other)
KW  - circuits (Other)
KW  - development (Other)
KW  - dopaminergic neurons (Other)
KW  - iPSCs (Other)
KW  - mouse (Other)
KW  - neurodegeneration (Other)
KW  - neuronal diversity (Other)
KW  - transcription factor (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:34525371
DO  - DOI:10.1016/j.celrep.2021.109697
UR  - https://pub.dzne.de/record/162865
ER  -