Abstract
Nurr1 and NGFI-B are closely related orphan members of the steroid-thyroid hormone receptor family involved in immediate early responses to stimuli such as growth factors. In-situ hybridization in the developing and adult mouse and rat demonstrated Nurr1 mRNA in several regions during early central nervous system (CNS) development. Expression persisted through the pre- and postnatal periods and was also found in several areas in the adult CNS. Positive areas include the olfactory bulb, parts of the cortex, the hippocampal formation and substantia nigra where Nurr1 and tyrosine hydroxylase mRNAs were co-expressed. 6-Hydroxydopamine-induced degeneration of mesencephalic dopamine neurons led to a corresponding loss of Nurr1 mRNA, demonstrating a link between Nurr1 and dopaminergic neurons. NGFI-B mRNA was not found in the prenatal CNS but was highly expressed in the adult brain in many areas including the olfactory bulb, cortex, basal ganglia and hippocampus. The spatiotemporal distribution of Nurr1 and NGFI-B mRNAs suggests that these transcription factors are involved in the development and maturation of specific sets of CNS neurons. The experimental data imply that one of these functions may be to control gene regulatory events important for development and function of those neurons that degenerate in patients with Parkinson's disease.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Animals, Newborn
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Brain / embryology
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Brain / growth & development
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Brain / metabolism*
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Corpus Striatum / drug effects
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Corpus Striatum / metabolism
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DNA-Binding Proteins / biosynthesis*
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DNA-Binding Proteins / genetics
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Dopamine / physiology*
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Enzyme Induction
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Fetal Proteins / biosynthesis
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Fetal Proteins / genetics
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Gene Expression Regulation, Developmental*
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Immediate-Early Proteins / biosynthesis*
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Immediate-Early Proteins / genetics
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In Situ Hybridization
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Mice
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Nerve Tissue Proteins / biosynthesis*
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Nerve Tissue Proteins / genetics
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Neurons / cytology
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Neurons / metabolism
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Nuclear Receptor Subfamily 4, Group A, Member 1
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Nuclear Receptor Subfamily 4, Group A, Member 2
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Organ Specificity
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Oxidopamine / toxicity
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Parkinson Disease / pathology
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RNA, Messenger / biosynthesis
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Rats
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Rats, Sprague-Dawley
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Receptors, Cytoplasmic and Nuclear
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Receptors, Steroid
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Spinal Cord / embryology
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Spinal Cord / growth & development
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Spinal Cord / metabolism
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Substantia Nigra / drug effects
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Substantia Nigra / metabolism
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Transcription Factors / biosynthesis*
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Transcription Factors / genetics
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Tyrosine 3-Monooxygenase / biosynthesis
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Tyrosine 3-Monooxygenase / genetics
Substances
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DNA-Binding Proteins
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Fetal Proteins
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Immediate-Early Proteins
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Nerve Tissue Proteins
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Nr4a1 protein, mouse
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Nr4a1 protein, rat
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Nr4a2 protein, mouse
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Nr4a2 protein, rat
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Nuclear Receptor Subfamily 4, Group A, Member 1
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Nuclear Receptor Subfamily 4, Group A, Member 2
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RNA, Messenger
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Receptors, Cytoplasmic and Nuclear
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Receptors, Steroid
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Transcription Factors
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Oxidopamine
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Tyrosine 3-Monooxygenase
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Dopamine