Abstract
BackgroundThe 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.ResultsWe 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.ConclusionWe 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.
Highlights
The homeobox containing transcription factor Uncx4.1 is, amongst others, expressed in the mouse midbrain
Uncx4.1 is expressed in the mantle layer of the developing midbrain In the central nervous system Uncx4.1 transcripts first appeared at E9.5 in the mesencephalon [10,13], but a detailed expression analysis of Uncx4.1 in the developing mouse midbrain at subsequent stages so far has not been performed
At all analyzed stages the expression of Uncx4.1 was similar throughout the rostral-caudal axis of the midbrain and it was excluded from the midbrain ventricular zone (VZ), suggesting that it is confined to postmitotic cells
Summary
The homeobox containing transcription factor Uncx4.1 is, amongst others, expressed in the mouse midbrain. 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. Uncx4.1 is a homeobox containing transcription factor with 88% identity to Unc from C.elegans [10,11]. In mice, it is expressed in the caudal half of the somite, the developing kidney, and the central nervous system [10,11]. The possible role of Uncx4.1 in the developing midbrain has not been addressed
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