Neuronal-Specific TUBB3 Is Not Required for Normal Neuronal Function but Is Essential for Timely Axon Regeneration

Alban Latremoliere, Long Cheng, Michelle DeLisle, Chen Wu, Sheena Chew, Elizabeth B. Hutchinson, Andrew Sheridan, Chloe Alexandre, Frederic Latremoliere, Shu Hsien Sheu, Sara Golidy, Takao Omura, Eric A. Huebner, Yanjie Fan, Mary C. Whitman, Elaine Nguyen, Crystal Hermawan, Carlo Pierpaoli, Max A. Tischfield, Clifford J. WoolfElizabeth C. Engle

Research output: Contribution to journalArticle

Abstract

We generated a knockout mouse for the neuronal-specific β-tubulin isoform Tubb3 to investigate its role in nervous system formation and maintenance. Tubb3 −/− mice have no detectable neurobehavioral or neuropathological deficits, and upregulation of mRNA and protein of the remaining β-tubulin isotypes results in equivalent total β-tubulin levels in Tubb3 −/− and wild-type mice. Despite similar levels of total β-tubulin, adult dorsal root ganglia lacking TUBB3 have decreased growth cone microtubule dynamics and a decreased neurite outgrowth rate of 22% in vitro and in vivo. The effect of the 22% slower growth rate is exacerbated for sensory recovery, where fibers must reinnervate the full volume of the skin to recover touch function. Overall, these data reveal that, while TUBB3 is not required for formation of the nervous system, it has a specific role in the rate of peripheral axon regeneration that cannot be replaced by other β-tubulins. Latremoliere et al. show that the neuronal-specific tubulin isoform TUBB3 is not required for normal development and function of the nervous system. Lack of TUBB3 decreases the dynamics of microtubules in growth cones, and this reduces axonal growth after peripheral nerve injury and strongly delays functional recovery.

Original languageEnglish (US)
Pages (from-to)1865-1879.e9
JournalCell Reports
Volume24
Issue number7
DOIs
StatePublished - Aug 14 2018

Keywords

  • TUBB3
  • axonal growth
  • development
  • diffusion tensor imaging
  • microtubule dynamics
  • mouse
  • post-translational modifications
  • sensory recovery
  • spot culture
  • tubulin

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Latremoliere, A., Cheng, L., DeLisle, M., Wu, C., Chew, S., Hutchinson, E. B., Sheridan, A., Alexandre, C., Latremoliere, F., Sheu, S. H., Golidy, S., Omura, T., Huebner, E. A., Fan, Y., Whitman, M. C., Nguyen, E., Hermawan, C., Pierpaoli, C., Tischfield, M. A., ... Engle, E. C. (2018). Neuronal-Specific TUBB3 Is Not Required for Normal Neuronal Function but Is Essential for Timely Axon Regeneration. Cell Reports, 24(7), 1865-1879.e9. https://doi.org/10.1016/j.celrep.2018.07.029