Aurora kinase B regulates axonal outgrowth and regeneration in the spinal motor neurons of developing zebrafish

Serene S. L. Gwee, Rowan A. W. Radford, Sharron Chow, Monisha D. Syal, Marco Morsch, Isabel Formella, Albert Lee, Emily K. Don, Andrew P. Badrock, Nicholas J. Cole, Adrian K. West, Steve N. S. Cheung, Roger S. Chung

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Abstract

Aurora kinase B (AurkB) is a serine/threonine protein kinase with a well-characterised role in orchestrating cell division and cytokinesis, and is prominently expressed in healthy proliferating and cancerous cells. However, the role of AurkB in differentiated and non-dividing cells has not been extensively explored. Previously, we have described a significant upregulation of AurkB expression in cultured cortical neurons following an experimental axonal transection. This is somewhat surprising, as AurkB expression is generally associated only with dividing cells Frangini et al. (Mol Cell 51:647–661, 2013); Hegarat et al. (J Cell Biol 195:1103–1113, 2011); Lu et al. (J Biol Chem 283:31785–31790, 2008); Trakala et al. (Cell Cycle 12:1030–1041, 2014). Herein, we present the first description of a role for AurkB in terminally differentiated neurons. AurkB was prominently expressed within post-mitotic neurons of the zebrafish brain and spinal cord. The expression of AurkB varied during the development of the zebrafish spinal motor neurons. Utilising pharmacological and genetic manipulation to impair AurkB activity resulted in truncation and aberrant motor axon morphology, while overexpression of AurkB resulted in extended axonal outgrowth. Further pharmacological inhibition of AurkB activity in regenerating axons delayed their recovery following UV laser-mediated injury. Collectively, these results suggest a hitherto unreported role of AurkB in regulating neuronal development and axonal outgrowth.
Original languageEnglish
Pages (from-to)4269-4285
Number of pages17
JournalCellular and Molecular Life Sciences
Volume75
Issue number23
Early online date21 Feb 2018
DOIs
Publication statusPublished - Dec 2018

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Keywords

  • Aurora kinase B
  • Zebrafish
  • Spinal motor neurons
  • Axonal outgrowth
  • Axonal regeneration

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