Prenatal ontogeny of tyrosine hydroxylase gene expression in the rat ventral mesencephalon

We have examined the development of dopaminergic (DA) neurons in the embryonic mesencephalon with regard to the expression of the gene coding for tyrosine hydroxylase (TH). Mesencephalic DA neurons from rat embryos aged E13 to E21 were analyzed using a quantitative in situ hybridization protocol featuring a 35S-labeled RNA probe complimentary to TH mRNA. In the early-to-mid stage embryonic brains, the expression of the TH gene was examined relative to the position of individual, migrating DA cells in the caudal-rostral and dorsal-ventral axes of the mesencephalon. In the later embryonic subjects, neurons were analyzed according to their position in one of the midbrain DA nuclei. The ontogeny of TH gene expression in the rat mesencephalon exhibited two phases: during the early phase (E13-E15), we observed major fluctuations in the level of TH gene expression accompanying the differentiation and maturation processes of the DA cells. Later, in the mid-to-late gestation 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 which characterize the ontogeny of TH gene expression in the prenatally developing mesencephalon, and suggest a connection between the maturational level of DA neurons and the expression of the key gene regulating their principle neurotransmitter.