The transcription factor BCL11A defines distinct subsets of midbrain dopaminergic neurons. Tolve et al.
Summary: Midbrain dopaminergic (mDA) neurons are diverse in their projection targets, impact 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 -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. Data description: each file contains raw data related to the indicated Figure of the Tolve et al. manuscript. Raw data are uncropped image files (.tif format) and/or excel tables with the quantifications that were used to create the graphs in the respective Figure. Figure 2 is based on data from Fernandes, H. et al. Single-Cell Transcriptomics of Parkinson’s Disease Human In Vitro Models Reveals Dopamine Neuron- Specific Stress Responses. Cell Reports 108263 (2020). Thus, we refer interested researchers to this publication for detailed data sets.