Differential expression of tyrosine hydroxylase in catecholaminergic neurons of neonatal wild-type and Nurr1-deficient mice.
The orphan nuclear receptor Nurr1 is a transcription factor that belongs to the steroid/thyroid hormone receptor superfamily and is expressed in many regions of the brain. To determine the physiological role of Nurr1, we previously generated mice with a null mutation in the Nurr1 gene. Nurr1-null mice appear to develop normally but die within 12 h after birth. Subsequent analysis revealed the absence of neurotransmitter dopamine and tyrosine hydroxylase immunoreactivity in the central dopaminergic area of newborn pups. Herein, using in situ hybridization histochemistry, we show that Nurr1 is expressed only in subset of catecholamine producing neurons (A2 partly, A8-A10 and A11 catecholaminergic cell groups), and is excluded from the norepinephrine producing neurons (A1, A2, A5-A6 catecholaminergic cell groups). Nurr1 was not expressed in the dopamine synthesizing cell groups (A12-A16 catecholaminergic cell groups) of the diencephalon and the olfactory bulb. As previously shown and confirmed in this study, tyrosine hydroxylase immunoreactivity was absent in the substantia nigra and ventral tegmental area of Nurr1-deficient mice. However, the loss of Nurr1 expression in A2 and A11 dopaminergic neurons did not affect their tyrosine hydroxylase immunoreactivity. This study begins to dissect cues necessary for understanding the complex regulation of the catecholaminergic biosynthetic pathway with regard to local, chemical and developmental changes in the brain.
Baffi
J S
JS
National Institutes of Health, Clinical Neuroscience Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA.
Palkovits
M
M
Castillo
S O
SO
Mezey
E
E
Nikodem
V M
VM
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001923:Brain Chemistry / Q000235:genetics / Q000502:physiology; D002395:Catecholamines / Q000502:physiology*; D004268:DNA-Binding Proteins; D004298:Dopamine / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics* / Q000502:physiology; D017403:In Situ Hybridization; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000235:genetics; D009474:Neurons / Q000201:enzymology*; D009638:Norepinephrine / Q000502:physiology; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis* / Q000235:genetics
D002395:Catecholamines; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C539883:Nr4a2 protein, mouse; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D012333:RNA, Messenger; D014157:Transcription Factors; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine; D009638:Norepinephrine