Open Access Highly Accessed Research article

The transcription factor Uncx4.1 acts in a short window of midbrain dopaminergic neuron differentiation

Tamara I Rabe12, Gundula Griesel1, Stephen Blanke1, Andreas Kispert3, Michael Leitges4, Bert van der Zwaag58, J Peter H Burbach5, Frédérique Varoqueaux6 and Ahmed Mansouri127*

Author Affiliations

1 Department of Molecular Cell Biology, Max Planck Institute of Biophysical Chemistry, Am Fassberg 11, Goettingen, 37077, Germany

2 DFG Research Center for the Molecular Physiology of the Brain, CMPB, Humboldtallee 23, Goettingen, 37073, Germany

3 Medizinische Hochschule Hannover, Institute of Molecular Biology, Carl Neuberg Strasse 1, Hannover, 30625, Germany

4 Biotechnology Centre of Oslo, University of Oslo, Gaustadalleen 21, Oslo, 0349, Norway

5 Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Department of Neuroscience and Pharmacology, Universiteitsweg 100, Utrecht, 3584 CG, The Netherlands

6 Department of Molecular Neurobiology, Max Planck Institute for Experimental Medicine, Hermann-Rein-Strasse 3, Goettingen, 37075, Germany

7 Department of Clinical Neurophysiology, University of Goettingen, Robert-Koch-Strasse 40, Göttingen, 37075, Germany

8 Current affiliation: Department of Biomedical Genetics, University Medical Center Utrecht, Universiteitsweg 100, Utrecht, 3584 CG, The Netherlands

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Neural Development 2012, 7:39  doi:10.1186/1749-8104-7-39

Published: 8 December 2012



The homeobox containing transcription factor Uncx4.1 is, amongst others, expressed in the mouse midbrain. The early expression of this transcription factor in the mouse, as well as in the chick midbrain, points to a conserved function of Uncx4.1, but so far a functional analysis in this brain territory is missing. The goal of the current study was to analyze in which midbrain neuronal subgroups Uncx4.1 is expressed and to examine whether this factor plays a role in the early development of these neuronal subgroups.


We have shown that Uncx4.1 is expressed in GABAergic, glutamatergic and dopaminergic neurons in the mouse midbrain. In midbrain dopaminergic (mDA) neurons Uncx4.1 expression is particularly high around E11.5 and strongly diminished already at E17.5. The analysis of knockout mice revealed that the loss of Uncx4.1 is accompanied with a 25% decrease in the population of mDA neurons, as marked by tyrosine hydroxylase (TH), dopamine transporter (DAT), Pitx3 and Ngn2. In contrast, the number of glutamatergic Pax6-positive cells was augmented, while the GABAergic neuron population appears not affected in Uncx4.1-deficient embryos.


We conclude that Uncx4.1 is implicated in the development of mDA neurons where it displays a unique temporal expression profile in the early postmitotic stage. Our data indicate that the mechanism underlying the role of Uncx4.1 in mDA development is likely related to differentiation processes in postmitotic stages, and where Ngn2 is engaged. Moreover, Uncx4.1 might play an important role during glutamatergic neuronal differentiation in the mouse midbrain.

Uncx4.1; Midbrain; mDA neurons; Ngn2; Pax6; Differentiation; Expression