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

Cell reports 2021 Sep 14

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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. Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.

Citation

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. 2021 Sep 14;36(11):109697