Sox6 and Otx2 control the specification of substantia nigra and ventral tegmental area dopamine neurons

Lia Panman, Maria Papathanou, Ariadna Laguna, Tony Oosterveen, Nikolaos Volakakis, Dario Acampora, Idha Kurtsdotter, Takashi Yoshitake, Jan Kehr, Eliza Joodmardi, Jonas Muhr, Antonio Simeone, Johan Ericson, Thomas Perlmann

Research output: Contribution to journalArticle

Abstract

Distinct midbrain dopamine (mDA) neuron subtypes are found in the substantia nigra pars compacta (SNc) and the ventral tegmental area (VTA), but it is mainly SNc neurons that degenerate in Parkinson's disease. Interest in how mDA neurons develop has been stimulated by the potential use of stem cells in therapy or disease modeling. However, very little is known about how specific dopaminergic subtypes are generated. Here, we show that the expression profiles of the transcription factors Sox6, Otx2, andNolz1 define subpopulations of mDA neurons already at the neural progenitor cell stage. After cell-cycle exit, Sox6 selectively localizes to SNc neurons, while Otx2 and Nolz1 are expressed in a subsetof VTA neurons. Importantly, Sox6 ablation leads todecreased expression of SNc markers and a corresponding increase in VTA markers, while Otx2 ablation has the opposite effect. Moreover, deletion of Sox6 affects striatal innervation and dopamine levels. We also find reduced Sox6 levels in Parkinson's disease patients. These findings identify Sox6 as a determinant of SNc neuron development and should facilitate the engineering of relevant mDA neurons for cell therapy and disease modeling.

Original languageEnglish
Pages (from-to)1018-1025
Number of pages8
JournalCell Reports
Volume8
Issue number4
DOIs
Publication statusPublished - Aug 21 2014

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Panman, L., Papathanou, M., Laguna, A., Oosterveen, T., Volakakis, N., Acampora, D., Kurtsdotter, I., Yoshitake, T., Kehr, J., Joodmardi, E., Muhr, J., Simeone, A., Ericson, J., & Perlmann, T. (2014). Sox6 and Otx2 control the specification of substantia nigra and ventral tegmental area dopamine neurons. Cell Reports, 8(4), 1018-1025. https://doi.org/10.1016/j.celrep.2014.07.016