PUBLICATION
NR4A2 controls the differentiation of selective dopaminergic nuclei in the zebrafish brain
- Authors
- Blin, M., Norton, W., Bally-Cuif, L., and Vernier, P.
- ID
- ZDB-PUB-081001-15
- Date
- 2008
- Source
- Molecular and cellular neurosciences 39(4): 592-604 (Journal)
- Registered Authors
- Bally-Cuif, Laure, Blin, Maryline, Norton, Will, Vernier, Philippe
- Keywords
- none
- MeSH Terms
-
- Animals
- Apoptosis
- Brain/anatomy & histology
- Brain/physiology*
- Catecholamines/metabolism
- Cell Differentiation*
- DNA-Binding Proteins/classification
- DNA-Binding Proteins/genetics
- DNA-Binding Proteins/metabolism*
- Dopamine/metabolism*
- Dopamine Antagonists/metabolism
- Gene Expression Regulation, Developmental
- Haloperidol/metabolism
- Humans
- In Situ Nick-End Labeling
- Mice
- Motor Activity
- Neurons/cytology
- Neurons/metabolism*
- Nuclear Receptor Subfamily 4, Group A, Member 2
- Phylogeny
- Proliferating Cell Nuclear Antigen/metabolism
- Stem Cells/cytology
- Stem Cells/physiology
- Transcription Factors/classification
- Transcription Factors/genetics
- Transcription Factors/metabolism*
- Tyrosine 3-Monooxygenase/genetics
- Tyrosine 3-Monooxygenase/metabolism
- Zebrafish
- PubMed
- 18822380 Full text @ Mol. Cell Neurosci.
Citation
Blin, M., Norton, W., Bally-Cuif, L., and Vernier, P. (2008) NR4A2 controls the differentiation of selective dopaminergic nuclei in the zebrafish brain. Molecular and cellular neurosciences. 39(4):592-604.
Abstract
The orphan nuclear receptor NR4A2/Nurr1 is mandatory for the terminal differentiation of mesencephalic dopamine neurons in mammals, but a similar role has remained elusive in the homologous area of the fish brain, the posterior tuberculum. Using loss- and gain-of-function experiments in zebrafish, we show that NR4A2 is indeed responsible for the expression of tyrosine hydroxylase (TH) in selective subpopulations of dopamine cells in the posterior tuberculum, as well as in the pretectum, preoptic area and telencephalon. Cross sections of the neural tube reveal that cells expressing the proliferation marker PCNA, NR4A2 and TH are aligned along a mediolateral progression rather than overlapping populations, suggesting that NR4A2 does not simply regulate TH expression but also controls more general steps of progenitor commitment towards the fully differentiated DA neuronal state. Finally, in line with NR4A2+/- heterozygote mice, NR4A2 morphant fish are hyperactive. This behavioural phenotype is maintained throughout life, pointing to a developmental control of locomotor activity by NR4A2. Our results shed new light on NR4A2 function in the DA differentiation pathway, and stress the effect of DA dysregulation on the control of locomotor activity.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping