Role of DNA topoisomerase IIβ in neurite outgrowth

Alam Nur-E-Kamal, Sally Meiners, Ijaz Ahmed, Anna Azarova, Chao p. Lin, Yi Lisa Lyu, Leroy-Fong Liu

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Failure to establish neuromuscular junctions is a major phenotype of top2β knockout mice. However, the precise mechanism for this defect is not known. In the current study, we have investigated the role of TopIIβ in cultured neurons. We showed that the TopII inhibitor ICRF-193 significantly blocked neurite outgrowth and growth cone formation in cultured cerebellar granule neurons (CGNs), dorsal root ganglions (DRGs) and cortical neurons (CNs). In addition, ICRF-193 also blocked neurite outgrowth and growth cone formation of PC12 cells undergoing NGF-induced differentiation. Isolated cortical neurons from top2β knockout embryos elaborated shorter neurites than did those from their wild type counterparts, confirming the role of TopIIβ in neurite outgrowth. Together, these results demonstrate a critical role of TopIIβ in neurite outgrowth in cultured neurons. Furthermore, we demonstrated that neurons derived from top2β knockout mice failed to form contacts with muscle cells in co-cultures. These results suggest that the defect in establishing neuromuscular junctions in top2β knockout mice could be due to the lack of TopIIβ-mediated neurite outgrowth.

Original languageEnglish
Pages (from-to)50-60
Number of pages11
JournalBrain Research
Volume1154
Issue number1
DOIs
Publication statusPublished - Jun 18 2007
Externally publishedYes

Keywords

  • Differentiation
  • Gene regulation
  • Neurite outgrowth
  • Neurons
  • Topoisomerases

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology
  • Clinical Neurology
  • Neuroscience(all)

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  • Cite this

    Nur-E-Kamal, A., Meiners, S., Ahmed, I., Azarova, A., Lin, C. P., Lyu, Y. L., & Liu, L-F. (2007). Role of DNA topoisomerase IIβ in neurite outgrowth. Brain Research, 1154(1), 50-60. https://doi.org/10.1016/j.brainres.2007.04.029