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

Fingerprint

Tubulin
Axons
Regeneration
Neurology
Nervous System
Growth Cones
Microtubules
Cones
Protein Isoforms
Recovery
Peripheral Nerve Injuries
Touch
Spinal Ganglia
Growth
Knockout Mice
Skin
Up-Regulation
Maintenance
Messenger RNA
Fibers

Keywords

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Neuronal-Specific TUBB3 Is Not Required for Normal Neuronal Function but Is Essential for Timely Axon Regeneration. / Latremoliere, Alban; Cheng, Long; DeLisle, Michelle; Wu, Chen; Chew, Sheena; Hutchinson, Elizabeth B.; Sheridan, Andrew; Alexandre, Chloe; Latremoliere, Frederic; Sheu, Shu Hsien; Golidy, Sara; Omura, Takao; Huebner, Eric A.; Fan, Yanjie; Whitman, Mary C.; Nguyen, Elaine; Hermawan, Crystal; Pierpaoli, Carlo; Tischfield, Max A.; Woolf, Clifford J.; Engle, Elizabeth C.

In: Cell Reports, Vol. 24, No. 7, 14.08.2018, p. 1865-1879.e9.

Research output: Contribution to journalArticle

Latremoliere, A, Cheng, L, DeLisle, M, Wu, C, Chew, S, Hutchinson, EB, Sheridan, A, Alexandre, C, Latremoliere, F, Sheu, SH, Golidy, S, Omura, T, Huebner, EA, Fan, Y, Whitman, MC, Nguyen, E, Hermawan, C, Pierpaoli, C, Tischfield, MA, Woolf, CJ & Engle, EC 2018, 'Neuronal-Specific TUBB3 Is Not Required for Normal Neuronal Function but Is Essential for Timely Axon Regeneration', Cell Reports, vol. 24, no. 7, pp. 1865-1879.e9. https://doi.org/10.1016/j.celrep.2018.07.029
Latremoliere, Alban ; Cheng, Long ; DeLisle, Michelle ; Wu, Chen ; Chew, Sheena ; Hutchinson, Elizabeth B. ; Sheridan, Andrew ; Alexandre, Chloe ; Latremoliere, Frederic ; Sheu, Shu Hsien ; Golidy, Sara ; Omura, Takao ; Huebner, Eric A. ; Fan, Yanjie ; Whitman, Mary C. ; Nguyen, Elaine ; Hermawan, Crystal ; Pierpaoli, Carlo ; Tischfield, Max A. ; Woolf, Clifford J. ; Engle, Elizabeth C. / Neuronal-Specific TUBB3 Is Not Required for Normal Neuronal Function but Is Essential for Timely Axon Regeneration. In: Cell Reports. 2018 ; Vol. 24, No. 7. pp. 1865-1879.e9.
@article{8fc6becdcf2a45c1b676d77b09248d98,
title = "Neuronal-Specific TUBB3 Is Not Required for Normal Neuronal Function but Is Essential for Timely Axon Regeneration",
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.",
keywords = "axonal growth, development, diffusion tensor imaging, microtubule dynamics, mouse, post-translational modifications, sensory recovery, spot culture, TUBB3, tubulin",
author = "Alban Latremoliere and Long Cheng and Michelle DeLisle and Chen Wu and Sheena Chew and Hutchinson, {Elizabeth B.} and Andrew Sheridan and Chloe Alexandre and Frederic Latremoliere and Sheu, {Shu Hsien} and Sara Golidy and Takao Omura and Huebner, {Eric A.} and Yanjie Fan and Whitman, {Mary C.} and Elaine Nguyen and Crystal Hermawan and Carlo Pierpaoli and Tischfield, {Max A.} and Woolf, {Clifford J.} and Engle, {Elizabeth C.}",
year = "2018",
month = "8",
day = "14",
doi = "10.1016/j.celrep.2018.07.029",
language = "English (US)",
volume = "24",
pages = "1865--1879.e9",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "7",

}

TY - JOUR

T1 - Neuronal-Specific TUBB3 Is Not Required for Normal Neuronal Function but Is Essential for Timely Axon Regeneration

AU - Latremoliere, Alban

AU - Cheng, Long

AU - DeLisle, Michelle

AU - Wu, Chen

AU - Chew, Sheena

AU - Hutchinson, Elizabeth B.

AU - Sheridan, Andrew

AU - Alexandre, Chloe

AU - Latremoliere, Frederic

AU - Sheu, Shu Hsien

AU - Golidy, Sara

AU - Omura, Takao

AU - Huebner, Eric A.

AU - Fan, Yanjie

AU - Whitman, Mary C.

AU - Nguyen, Elaine

AU - Hermawan, Crystal

AU - Pierpaoli, Carlo

AU - Tischfield, Max A.

AU - Woolf, Clifford J.

AU - Engle, Elizabeth C.

PY - 2018/8/14

Y1 - 2018/8/14

N2 - 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.

AB - 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.

KW - axonal growth

KW - development

KW - diffusion tensor imaging

KW - microtubule dynamics

KW - mouse

KW - post-translational modifications

KW - sensory recovery

KW - spot culture

KW - TUBB3

KW - tubulin

UR - http://www.scopus.com/inward/record.url?scp=85051241212&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85051241212&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2018.07.029

DO - 10.1016/j.celrep.2018.07.029

M3 - Article

C2 - 30110642

AN - SCOPUS:85051241212

VL - 24

SP - 1865-1879.e9

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 7

ER -