Tyrosine hydroxylase is expressed by neocortical neurons after transplantation

Abstract

Tyrosine hydroxylase [TyrOHase; L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2], an essential enzyme in the synthesis of catecholamines, is expressed normally by neurons in the brainstem but not by those in mature neocortex. When embryonic neocortex is transplanted into adult neocortex, TyrOHase-immunoreactive cells develop and continue to be present in the transplants for the life of the host animal. The percentage of transplant neurons that express TyrOHase is highly correlated with the age of the embryonic donor tissue at the time of transplantation. Many TyrOHase-immunoreactive cells are present in transplants from embryonic day 12 (E12) embryos. The labeled cells are frequently arrayed in striking clusters of cell bodies and their processes, which ramify densely within the transplants. Moderate numbers of cells are found scattered throughout transplants from E14 donors, while E17 donors consistently develop small numbers of TyrOHase-containing cells. Tissue removed for transplantation on the day before birth (E19) never contains cells that express TyrOHase. The TyrOHase-positive cells are mostly bipolar and stellate in shape and show neither immunoreactivity for other catecholamine-synthesizing enzymes nor catecholamine fluorescence. These results provide a demonstration of continued TyrOHase synthesis in central nervous system cells that normally do not express this enzyme. Because of these and similar results with other neurotransmitter enzymes, the transplantation paradigm is particularly useful as a technique for studying the factors that regulate enzyme induction and activity during development of the nervous system.