Cited by 196Nuclear Receptors and SignalingNeurogenesis and neuroplasticity mechanismsDevelopmental Biology and Gene Regulation

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

Smits, Simone M., Ponnio, Tiia, Conneely, Orla M., Burbach, J. Peter H., Smidt, Marten P.·2003·European Journal of Neuroscience

DOI 10.1046/j.1460-9568.2003.02885.x

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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.

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Authors: Smits, S. M., Ponnio, T., Conneely, O. M., Burbach, J. P. H., & Smidt, M. P.
Affiliations: University Medical Center Utrecht (NL)
Baylor College of Medicine (US)
ORCID: Smits, Simone M.
Burbach, J. Peter H.
Smidt, Marten P.
Venue: European Journal of Neuroscience
Publisher: Wiley
Published: 2003-10
Volume: 18
Issue: 7
Pages: 1731-1738
ISSN: 0953-816X (ISSN-L)
1460-9568
DOI: 10.1046/j.1460-9568.2003.02885.x
OpenAlex: W1978387829
Cited by: 194
References: 47
Citations by year: 2026: 2 · 2025: 1 · 2024: 2 · 2023: 4 · 2022: 4 · 2021: 6 · 2020: 11 · 2019: 7 · 2018: 5 · 2017: 11 · 2016: 3 · 2015: 6 · 2014: 7 · 2013: 13 · 2012: 16
FWCI: 3.36
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 20 d)
Locations: European Journal of Neuroscience (publishedVersion)
PubMed (publishedVersion)
Funders: Nederlandse Organisatie voor Wetenschappelijk Onderzoek
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords: Nurr1, midbrain dopaminergic neurons, ventral midbrain, neurotransmitter identity, vesicular monoamine transporter 2, dopamine transporter, tyrosine hydroxylase, transcriptional regulation, embryonic development
MeSH terms: Animals, Animals, Newborn, Aromatic-L-Amino-Acid Decarboxylases, DNA-Binding Proteins, Dopamine, Immunohistochemistry, Membrane Glycoproteins, Mesencephalon, Mice, Inbred C57BL, Neurons, Neuropeptides, RNA, Messenger, Transcription Factors, Tyrosine 3-Monooxygenase, In Situ Hybridization, Mice, Knockout, Neurotransmitter Agents, Homeodomain Proteins, Reverse Transcriptase Polymerase Chain Reaction, Membrane Transport Proteins, Vesicular Biogenic Amine Transport Proteins, Vesicular Monoamine Transport Proteins, Mice, Nuclear Receptor Subfamily 4, Group A, Member 2

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

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