How dopamine producing neurons arise in the developing brain
In a new study from Karolinska Institutet, published in Nature Neuroscience, researchers have identified the neurogenic progenitor that give rise to dopaminergic neurons, the primary neurons affected in Parkinson’s disease. These findings could help improve how dopaminergic neurons are produced for transplantation in Parkinson’s disease.
The researchers also identified a second progenitor cell type that supports dopaminergic neuron development and survival. Dopaminergic neurons are essential for controlling movement and in Parkinson’s disease these neurons in the midbrain gradually degenerate and cannot regenerate on their own.
“One potential treatment now being tested in clinical trials is the transplantation of dopaminergic progenitors made from human stem cells. Improving cell transplantation depends on understanding how dopaminergic neurons normally develop. Our findings show how these neurons and their supporting environment are generated together during human brain development”, says Emilía Sif Ásgrímsdóttir, first author of the study and a former doctoral student at the Department of Medical Biochemistry and Biophysics at Karolinska Institutet.
Previous single-cell atlases of the developing human brain generated at Karolinska Institutet had revealed an unexpected diversity of midbrain progenitor cell types, but it remained unclear how this diversity contributes to dopaminergic neuron development. In this study, the researchers combined single‑cell genomic data with experiments in human stem cell models to functionally characterize these specialized progenitors.
The study builds on decades of research into dopaminergic neuron development and Parkinson’s disease led by the late Prof. Ernest Arenas. His work laid important foundations for understanding how dopaminergic neurons arise during midbrain development and continues to influence research in the field.
This research was supported by the Swedish Research Council, the Knut and Alice Wallenberg Foundation, the Swedish Foundation for Strategic Research among others. See the study for any reported conflicts of interest.
Publication
"Distinct radial glia subtypes regulate midbrain dopaminergic neuron development", Emilía Sif Ásgrímsdóttir, Luca Fusar Bassini, Ting Sun, Clàudia Puigsasllosas Pastor, Pia Rivetti di Val Cervo, Daniel Gyllborg, Kawai Lee, Christopher L. Grigsby, Baptiste Jude, Carmen Abaurre, Saiful Islam, Peter Lönnerberg, Carlos Villaescusa, Carmen Saltó, Roger A. Barker, Sten Linnarsson, Goncalo Castelo-Branco, Gioele La Manno, Enrique M. Toledo, Ernest Arenas. Nature Neuroscience, online 16 February 2026, doi: 10.1038/s41593-026-02200-8.