Nr4a2 is essential for the differentiation of dopaminergic neurons during zebrafish embryogenesis.
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.
Luo
Guang Rui
GR
Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Chen
Yi
Y
Li
Xu Ping
XP
Liu
Ting Xi
TX
Le
Wei Dong
WD
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D051792:Basic Helix-Loop-Helix Proteins; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D004625:Embryo, Nonmammalian; D047108:Embryonic Development / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D009419:Nerve Tissue Proteins; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D013477:Superior Colliculi / Q000166:cytology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics
D051792:Basic Helix-Loop-Helix Proteins; D001973:Bromodeoxyuridine; D004268:DNA-Binding Proteins; D004298:Dopamine; D050483:Dopamine Plasma Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D014157:Transcription Factors; D014446:Tyrosine 3-Monooxygenase; D029961:Zebrafish Proteins; C539883:Nr4a2 protein, mouse; C486337:neurog1 protein, zebrafish