Midbrain dopamine (mDA) neurons are produced by mDA progenitors during early development. Any progenitor cells that remain after this neurogenic period exit the cell cycle and begin to mature into the multi-ciliated ependymal cells that line the brain ventricles. mDA neuron degeneration contributes to mobility problems in Parkinson’s disease, so understanding mDA progenitor differentiation could help inform future treatments. Here, Laura Lahti, Thomas Perlmann and colleagues investigate how the timing of mDA neuron production is regulated in the developing mouse brain. They re-analyse their existing single-cell RNA sequencing data and find that late-stage mDA progenitors express higher levels of Nfib and Sox9 than early-stage mDA progenitors. Nfib and Sox9 encode transcription factors with known roles in neurogenesis, and the authors find that depletion of Nfib, Nfix and Sox9 in the midbrain postpones, but does not prevent, cell cycle exit in the mDA progenitors. This perturbation results in a prolonged period of neurogenesis, thus producing more mDA neurons and delaying the maturation of ependymal cells. The authors go on to detect a subpopulation of ependymal cells that express markers associated with progenitor properties; these ependymal cells do not proliferate in vivo but can do so under certain in vitro conditions. Overall, this study provides insight into the molecular mechanisms that regulate mDA progenitor differentiation and offers future avenues in the search for Parkinson’s disease treatments.
