Differential expressions of the topoisomerase II alpha and II beta mRNAs in developing rat brain.

Distributions of the topoisomerase II alpha and II beta mRNAs were examined in the developing rat brain, by in situ hybridization with isoform-specific oligonucleotide probes. Intense signals for the topoisomerase II alpha mRNA were detected in the ventricular zone of each brain region at embryonic day 13-15 (E13-E15), and in the external granular layer of the cerebellum at postnatal day 7-14 (P7-P14). Thereafter, the signals rapidly decreased in levels and eventually disappeared from respective regions. Administration of bromodeoxyuridine (BrdU) into embryos at E13 showed that the topoisomerase II alpha mRNA was expressed in the BrdU-incorporated region and its ventricular side of the neural wall, suggesting that transcription of this isoform occurs in neurons from S-phase through M-phase. On the other hand, the topoisomerase II beta mRNA was distributed throughout the brain from E13 through P21, irrespective of the ventricular and mantle zones. Signal levels of the topoisomerase II beta mRNA were much stronger during early developmental stages than at mature stages in various brain regions. The characteristic and differential spatio-temporal expressions suggest that the topoisomerase II alpha is involved in the proliferation, while the topoisomerase II beta is closely related to differentiation and maturation of neurons.