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

Authors

• Alban Latremoliere, Kirby Neurobiology Center, Boston Children’s Hospital, Harvard Medical School, Johns Hopkins School of Medicine
• Long Cheng, Kirby Neurobiology Center, Boston Children’s Hospital, Boston Children’s Hospital, Harvard Medical School
• Michelle DeLisle, Kirby Neurobiology Center, Boston Children’s Hospital, Boston Children’s Hospital, Howard Hughes Medical Institute
• Chen Wu, Kirby Neurobiology Center, Boston Children’s Hospital, Boston Children’s Hospital, Harvard Medical School
• Sheena Chew, Kirby Neurobiology Center, Boston Children’s Hospital, Boston Children’s Hospital, Howard Hughes Medical Institute
• Elizabeth B. Hutchinson, Quantitative Medical Imaging Section, National Institute of Biomedical Imaging and Bioengineering, NIH, The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc.
• Andrew Sheridan, Boston Children’s Hospital
• Chloe Alexandre, Beth Israel Deaconess Medical Center, Harvard Medical School
• Frederic Latremoliere, University of DenverFollow
• Shu-Hsien Sheu, Boston Children’s Hospital
• Sara Golidy, Boston Children’s Hospital, Howard Hughes Medical Institute
• Takao Omura, Kirby Neurobiology Center, Boston Children’s Hospital, Harvard Medical School, Hamamatsu University School of Medicine
• Eric A. Huebner, Kirby Neurobiology Center, Boston Children’s Hospital, Harvard Medical School
• Yanjie Fan, Kirby Neurobiology Center, Boston Children’s Hospital, Boston Children’s Hospital, Harvard Medical School
• Mary C. Whitman, Kirby Neurobiology Center, Boston Children’s Hospital, Boston Children’s Hospital, Harvard Medical School
• Elaine Nguyen, Kirby Neurobiology Center, Boston Children’s Hospital, Boston Children’s Hospital
• Crystal Hermawan, Kirby Neurobiology Center, Boston Children’s Hospital, Boston Children’s Hospital
• Carlo Pierpaoli, Quantitative Medical Imaging Section, National Institute of Biomedical Imaging and Bioengineering, NIH, The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc.
• Max A. Tischfield, Kirby Neurobiology Center, Boston Children’s Hospital, Boston Children’s Hospital, Harvard Medical School
• Clifford J. Woolf, Kirby Neurobiology Center, Boston Children’s Hospital, Harvard Medical School
• Elizabeth C. Engle, Kirby Neurobiology Center, Boston Children’s Hospital, Boston Children’s Hospital, Boston Children’s Hospital, Harvard Medical School, Howard Hughes Medical Institute

Publication Date

8-20-2018

Document Type

Article

Organizational Units

Mathematics

Keywords

Tubulin, TUBB3, Development, Mouse, Axonal growth, Microtubule dynamics, Sensory recovery, Spot culture, Post-translational modifications, Diffusion tensor imaging

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.

Publication Statement

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Recommended Citation

Latremoliere, Alban, et al. “Neuronal-Specific TUBB3 Is Not Required for Normal Neuronal Function but Is Essential for Timely Axon Regeneration.” Cell Reports (Cambridge), vol. 24, no. 7, 2018, pp. 1865–1879.e9. doi: 10.1016/j.celrep.2018.07.029.