title: The transcription factor Uncx4.1 acts in a short window of midbrain dopaminergic neuron differentiation.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Molecular Cell Biology, Max Planck Institute of Biophysical Chemistry, Am Fassberg 11, Goettingen, 37077, Germany.
authors.forename: Tamara I
authors.initials: TI
authors.lastname: Rabe
authors.forename: Gundula
authors.initials: G
authors.lastname: Griesel
authors.forename: Stephen
authors.initials: S
authors.lastname: Blanke
authors.forename: Andreas
authors.initials: A
authors.lastname: Kispert
authors.forename: Michael
authors.initials: M
authors.lastname: Leitges
authors.forename: Bert
authors.initials: B
authors.lastname: van der Zwaag
authors.forename: J Peter H
authors.initials: JP
authors.lastname: Burbach
authors.forename: Frédérique
authors.initials: F
authors.lastname: Varoqueaux
authors.forename: Ahmed
authors.initials: A
authors.lastname: Mansouri
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count; D016923:Cell Death / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000502:physiology*; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D047468:Immunoprecipitation; D020287:In Situ Nick-End Labeling; D008636:Mesencephalon / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D001973:Bromodeoxyuridine; D050483:Dopamine Plasma Membrane Transport Proteins; D049452:Green Fluorescent Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D014446:Tyrosine 3-Monooxygenase; C102938:Neurog2 protein, mouse; C108545:Uncx4.1 protein, mouse