PUBLICATION

Nr4a2 is essential for the differentiation of dopaminergic neurons during zebrafish embryogenesis

Authors

Luo, G.R., Chen, Y., Li, X.P., Liu, T.X., and Le, W.D.

ID

ZDB-PUB-080722-25

Date

2008

Source

Molecular and cellular neurosciences 39(2): 202-210 (Journal)

Registered Authors

Chen, Yi, Liu, Ting Xi

Keywords

nr4a2, DA progenitors, zebrafish

MeSH Terms

Neurons/physiology*
Apoptosis/physiology
Zebrafish Proteins/genetics
Tyrosine 3-Monooxygenase/genetics
Tyrosine 3-Monooxygenase/metabolism
Gene Expression Regulation, Developmental/physiology
DNA-Binding Proteins/genetics
DNA-Binding Proteins/physiology*
Transcription Factors/genetics
Transcription Factors/physiology*
Basic Helix-Loop-Helix Transcription Factors
Nuclear Receptor Subfamily 4, Group A, Member 2
Dopamine/metabolism*
Superior Colliculi/cytology
Embryo, Nonmammalian
Bromodeoxyuridine/metabolism
Dopamine Plasma Membrane Transport Proteins/metabolism
Cell Differentiation/genetics
Cell Differentiation/physiology*
Embryonic Development/genetics
Embryonic Development/physiology*
Animals
Nerve Tissue Proteins
Zebrafish/genetics
Zebrafish/metabolism
Neurogenesis/genetics
Neurogenesis/physiology*

(all 27)

PubMed

18638558 Full text @ Mol. Cell Neurosci.

Abstract

Nr4a2 is a member of the orphan nuclear receptor gene superfamily, which has been found to be critical for the development and maintenance of mesencephalic dopaminergic (DA) neurons. To uncover the molecular mechanisms by which Nr4a2 contributes to the development of DA neurons, we have applied zebrafish to study the topographic distribution of nr4a2b transcripts, as well as its correlation with neuronal progenitor marker (neurogenin 1) and DA neuron markers (tyrosine hydroxylase, TH and DA transporter, DAT) during neurogenesis. Our studies showed that although nr4a2b transcripts did not co-localize with TH and DAT transcripts in the posterior tuberculum (PT area), knockdown of Nr4a2 resulted in a significant decrease of TH(+) and DAT(+) DA neurons in the PT area, accompanied by a reduction of DA transmitter, which were partially rescued by the injection of mouse Nr4a2 mRNA. Surprisingly, the number of nr4a2b(+) cells in Nr4a2-deficient embryos was increased by 1.6 fold. These results suggest that Nr4a2 may play an important role in the differentiation and maturation rather than the survival of DA progenitors in the PT area during zebrafish early embryogenesis.

Genes / Markers

Figures

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Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
neurog1	WT	standard conditions	Long-pec	forebrain	ISH	Fig. 3
neurog1	WT	standard conditions	Prim-25	forebrain	ISH	Fig. 3
neurog1	WT	standard conditions	Prim-5	forebrain	ISH	Fig. 3
nr4a2a	WT	control	Long-pec	whole organism	RTPCR	Fig. S3
nr4a2a	WT + MO2-nr4a2a	standard conditions	Long-pec	whole organism	RTPCR	Fig. S3
nr4a2a	WT + MO2-nr4a2a,nr4a2b	standard conditions	Long-pec	whole organism	RTPCR	Fig. S3
nr4a2a	WT + MO2-nr4a2b	standard conditions	Long-pec	whole organism	RTPCR	Fig. S3
nr4a2b	WT	standard conditions	Prim-25	caudal tuberculum	ISH	Fig. 1
nr4a2b	WT	standard conditions	Prim-25	caudal tuberculum	ISH	Fig. 2
nr4a2b	WT	standard conditions	Prim-5	caudal tuberculum	ISH	Fig. 1

1 - 10 of 82

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT + MO2-nr4a2a	standard conditions	Long-pec	caudal tuberculum adrenergic neuron decreased amount, abnormal	Fig. 4
WT + MO2-nr4a2a	standard conditions	Long-pec	forebrain neuron development disrupted, abnormal	Fig. 4
WT + MO2-nr4a2a	standard conditions	Long-pec	olfactory bulb adrenergic neuron decreased amount, abnormal	Fig. 4
WT + MO2-nr4a2a	standard conditions	Long-pec	preoptic area adrenergic neuron decreased amount, abnormal	Fig. 4
WT + MO2-nr4a2a	standard conditions	Long-pec	pretectum adrenergic neuron decreased amount, abnormal	Fig. 4
WT + MO2-nr4a2a,nr4a2b	standard conditions	Long-pec	caudal tuberculum adrenergic neuron decreased amount, abnormal	Fig. 4
WT + MO2-nr4a2a,nr4a2b	standard conditions	Long-pec	forebrain adrenergic neuron decreased amount, abnormal	Fig. 5
WT + MO2-nr4a2a,nr4a2b	standard conditions	Long-pec	forebrain neuron development disrupted, abnormal	Fig. 4
WT + MO2-nr4a2a,nr4a2b	standard conditions	Long-pec	forebrain neuron development disrupted, abnormal	Fig. 5
WT + MO2-nr4a2a,nr4a2b	standard conditions	Long-pec	olfactory bulb adrenergic neuron decreased amount, abnormal	Fig. 4

1 - 10 of 17

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Mutations / Transgenics

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
nr4a2a	MO2-nr4a2a	MRPHLNO
nr4a2a	MO2-nr4a2a,nr4a2b	MRPHLNO
nr4a2b	MO2-nr4a2b	MRPHLNO
nr4a2b	MO2-nr4a2a,nr4a2b	MRPHLNO

Fish

Fish
WT
WT + MO2-nr4a2a
WT + MO2-nr4a2a,nr4a2b
WT + MO2-nr4a2b

Antibodies

Name	Type	Antigen Genes	Isotypes	Host Organism
Ab3-th	monoclonal	th	IgG1	Mouse

Orthology

Gene	Orthology
nr4a2b

Engineered Foreign Genes

Mapping

Luo et al., 2008 ZDB-PUB-080722-25 PMID:18638558

Nr4a2 is essential for the differentiation of dopaminergic neurons during zebrafish embryogenesis

Luo et al., 2008

ZDB-PUB-080722-25
PMID:18638558