Immunohistochemical analyses of DNA topoisomerase II isoforms in developing rat cerebellum

Kimiko Tsutsui, Ken Tsutsui, Osamu Hosoya, Kuniaki Sano, Akira Tokunaga

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52 Citations (Scopus)


In mammalian cells, two isoforms of DNA topoisomerase II (topo IIα and topo IIβ) have been identified. Topo IIα is essential in mitotic cells, whereas the function of topo IIβ remains unclear. In the present study, we investigated the developmental control of topo II isoforms in two different neuronal lineages, cerebellar Purkinje cells and granule cells, by immunohistochemical analysis with isoform-specific monoclonal antibodies. As expected, proliferating cells in the neuroepithelium and in the external germinal layer (EGL) were topo IIα immunopositive. The migrating as well as differentiating Purkinje cells and granule cells showed an enhanced topo IIβ immunoreactivity. The postmitotic granule cells in the postnatal EGL showed an abrupt transition of expressed topo II isoforms from IIα to IIβ. The transition was clearly coincident with the completion of final cell division and the initiation of terminal differentiation because no increase of the topo IIβ immunoreactivity was observed in the spreading EGL cells that are still in the cell division cycle. The topo IIβ signal was detected in both nucleoplasm and nucleolus of differentiating cells. However, the nucleoplasmic signal decreased significantly as the cells reached terminal differentiation. The residual topo IIβ in nucleoli was shown to occupy an unique location with respect to other nucleolar proteins, nucleolin and DNA topoisomerase I. Our findings indicate that both Purkinje cells and granule cells express the topo II isoforms in a similar timing during the cerebellar development and also suggest that topo IIβ localized in nucleoplasm is the functional entity involved in neuronal differentiation.

Original languageEnglish
Pages (from-to)228-239
Number of pages12
JournalJournal of Comparative Neurology
Issue number2
Publication statusPublished - Mar 5 2001


  • Confocal microscopy
  • Granule cells
  • Neuronal differentiation
  • Nucleolus
  • Purkinje cells
  • Topoisomerase IIβ

ASJC Scopus subject areas

  • General Neuroscience


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