PRENATAL ONTOGENY OF TYROSINE-HYDROXYLASE GENE-EXPRESSION IN THE RAT VENTRAL MESENCEPHALON

We have examined the development of dopaminergic (DA) neurons in the e mbryonic mesencephalon with regard to the expression of the gene codin g for tyrosine hydroxylase (TH). Mesencephalic DA neurons from rat emb ryos aged E13 to E21 were analyzed using a quantitative in situ hybrid ization protocol featuring a S-35-labeled RNA probe complimentary to T H mRNA. In the early-to-mid stage embryonic brains, the expression of the TH gene was examined relative to the position of individual, migra ting DA cells in the caudal-rostral and dorsal-ventral axes of the mes encephalon. In the later embryonic subjects, neurons were analyzed acc ording to their position in one of the midbrain DA nuclei. The ontogen y of TH gene expression in the rat mesencephalon exhibited two phases: during the early phase (E13-E15), we observed major fluctuations in t he level of TH gene expression accompanying the differentiation and ma turation processes of the DA cells. Later, in the mid-to-late gestatio n fetus (E18-E21), TH gene expression generally stabilized as TH mRNA- expressing neurons reached their final anatomical positions within the mesencephalic DA complex. Our data demonstrate the complex dynamics w hich characterize the ontogeny of TH gene expression in the prenatally developing mesencephalon, and suggest a connection between the matura tional level of DA neurons and the expression of the key gene regulati ng their principle neurotransmitter.