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
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.
