Involvement of Nurr1 in specifying the neurotransmitter identity of ventral midbrain dopaminergic neurons

Involvement of Nurr1 in specifying the neurotransmitter identity of ventral midbrain dopaminergic... The mesencephalic dopaminergic (mesDA) system is involved in many brain functions including motor control and motivated behaviour, and is of clinical importance because of its implication in psychiatric disorders and Parkinson's disease. Nurr1, a member of the nuclear hormone receptor superfamily of transcription factors, is essential for establishing the dopaminergic phenotype, because expression of tyrosine hydroxylase (TH), the rate‐limiting enzyme in dopamine synthesis, requires Nurr1. In addition, Nurr1 plays an important role in the maintenance of mesDA neurons. Neonatal Nurr1 knockout mice lack expression of the dopamine transporter (DAT), the vesicular monoamine transporter 2 (VMAT2) and l‐aromatic amino acid decarboxylase (AADC) in addition to TH specifically in mesDA neurons. It is unclear whether the lack of expression of these dopaminergic markers is caused by a maintenance defect or whether the induction of these markers depends on Nurr1 expression. To address this problem, the expression of DAT, VMAT2 and AADC was analysed at embryonic day 12.5 and 14.5. Here we demonstrate that induction of VMAT2 and DAT specifically in mesDA neurons requires Nurr1 expression, whereas AADC expression in mesDA neurons is induced independently of Nurr1 function. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Neuroscience Wiley

Involvement of Nurr1 in specifying the neurotransmitter identity of ventral midbrain dopaminergic neurons

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Publisher
Wiley
Copyright
Copyright © 2003 Wiley Subscription Services, Inc., A Wiley Company
ISSN
0953-816X
eISSN
1460-9568
DOI
10.1046/j.1460-9568.2003.02885.x
Publisher site
See Article on Publisher Site

Abstract

The mesencephalic dopaminergic (mesDA) system is involved in many brain functions including motor control and motivated behaviour, and is of clinical importance because of its implication in psychiatric disorders and Parkinson's disease. Nurr1, a member of the nuclear hormone receptor superfamily of transcription factors, is essential for establishing the dopaminergic phenotype, because expression of tyrosine hydroxylase (TH), the rate‐limiting enzyme in dopamine synthesis, requires Nurr1. In addition, Nurr1 plays an important role in the maintenance of mesDA neurons. Neonatal Nurr1 knockout mice lack expression of the dopamine transporter (DAT), the vesicular monoamine transporter 2 (VMAT2) and l‐aromatic amino acid decarboxylase (AADC) in addition to TH specifically in mesDA neurons. It is unclear whether the lack of expression of these dopaminergic markers is caused by a maintenance defect or whether the induction of these markers depends on Nurr1 expression. To address this problem, the expression of DAT, VMAT2 and AADC was analysed at embryonic day 12.5 and 14.5. Here we demonstrate that induction of VMAT2 and DAT specifically in mesDA neurons requires Nurr1 expression, whereas AADC expression in mesDA neurons is induced independently of Nurr1 function.

Journal

European Journal of NeuroscienceWiley

Published: Oct 1, 2003

References

  • A selective group of dopaminergic neurons express Nurr1 in the adult mouse brain
    Bäckman, Bäckman; Perlman, Perlman; Wallén, Wallén; Hoffer, Hoffer; Morales, Morales
  • Dopamine biosynthesis is selectively abolished in substantia nigra/ventral tegmental area but not in hypothalamic neurons in mice with targeted disruption of the Nurr1 gene
    Castillo, Castillo; Baffi, Baffi; Palkovits, Palkovits; Goldstein, Goldstein; Kopin, Kopin; Witta, Witta; Magnuson, Magnuson; Nikodem, Nikodem
  • Re‐evaluation of the role of the dopamine transporter in dopamine system homeostasis
    Gainetdinov, Gainetdinov; Jones, Jones; Fumagalli, Fumagalli; Wightman, Wightman; Caron, Caron
  • Specification of dopaminergic and serotonergic neurons in the vertebrate CNS
    Hynes, Hynes; Rosenthal, Rosenthal
  • Differential regulation of tyrosine hydroxylase in the basal ganglia of mice lacking the dopamine transporter
    Jaber, Jaber; Dumartin, Dumartin; Sagne, Sagne; Haycock, Haycock; Roubert, Roubert; Giros, Giros; Bloch, Bloch; Caron, Caron

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