Ontogenetic changes in laminar distribution of ornithine decarboxylase during development of cerebellar cortex: autoradiographic localization with [3H]alpha-difluoromethylornithine.

Ornithine decarboxylase is the first enzyme in the biosynthesis of the polyamines, which control macromolecule synthesis during cellular development. Polyamines appear to play a critical role in the development of the rat cerebellar cortex, since postnatal treatment with the specific irreversible ornithine decarboxylase inhibitor, alpha-difluoromethylornithine, arrests cell division and migration in this region. To determine whether the distribution of ornithine decarboxylase within the developing cerebellar cortex correlates with specific maturational events, [3H]alpha-difluoromethylornithine, a specific marker for ornithine decarboxylase activity, was localized autoradiographically in 3-13-day-old rats. The density of autoradiographic grains within the cerebellar cortex as a whole paralleled the postnatal rise and fall of biochemically determined ornithine decarboxylase activity. Superimposed on this pattern was a selective laminar distribution of label which indicated specific association of ornithine decarboxylase with cell replication, as shown by preferential labeling of the superficial (mitotic) zone of the external granule cell layer. In addition, ornithine decarboxylase activity was temporally associated with regions in which post-mitotic cells were undergoing migration, axonogenesis and dendritic arborization, as shown by the patterns obtained in deeper layers. In contrast, there was no evidence for an association between ornithine decarboxylase activity and synaptogenesis, gliogenesis or myelination. These results, in combination with previous biochemical and morphological data, support the view that the ornithine decarboxylase/polyamine system plays an important role in both mitotic and post-mitotic events within the nervous system.