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Kumamoto K, Iguchi T, Ishida R, et al. Developmental downregulation of LIS1 expression limits axonal extension and allows axon pruning. Biol Open. 2017;6(7):1041-1055doi: 10.1242/bio.025999.
Kumamoto, K., Iguchi, T., Ishida, R., Uemura, T., Sato, M., & Hirotsune, S. (2017). Developmental downregulation of LIS1 expression limits axonal extension and allows axon pruning. Biology open, 6(7), 1041-1055. https://doi.org/10.1242/bio.025999
Kumamoto, Kanako, et al. "Developmental downregulation of LIS1 expression limits axonal extension and allows axon pruning." Biology open vol. 6,7 (2017): 1041-1055. doi: https://doi.org/10.1242/bio.025999
Kumamoto K, Iguchi T, Ishida R, Uemura T, Sato M, Hirotsune S. Developmental downregulation of LIS1 expression limits axonal extension and allows axon pruning. Biol Open. 2017 Jul 15;6(7):1041-1055. doi: 10.1242/bio.025999. PMID: 28630356; PMCID: PMC5550919.
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Biol Open. 2017 Jul 15;6(7):1041-1055. doi: 10.1242/bio.025999.

Developmental downregulation of LIS1 expression limits axonal extension and allows axon pruning.

Biology open

Kanako Kumamoto, Tokuichi Iguchi, Ryuichi Ishida, Takuya Uemura, Makoto Sato, Shinji Hirotsune

Affiliations

  1. Department of Genetic Disease Research, Osaka City University, Graduate School of Medicine, Asahi-machi 1-4-3, Abeno, Osaka 545-8585, Japan.
  2. Department of Anatomy and Neuroscience, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
  3. Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, Asahi-machi 1-4-3, Abeno, Osaka 545-8585, Japan.
  4. Research Center for Child Mental Development, University of Fukui, Fukui 910-1193, Japan.
  5. United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University, and University of Fukui, Osaka 565-0871, Japan.
  6. Department of Genetic Disease Research, Osaka City University, Graduate School of Medicine, Asahi-machi 1-4-3, Abeno, Osaka 545-8585, Japan [email protected].

PMID: 28630356 PMCID: PMC5550919 DOI: 10.1242/bio.025999

Abstract

The robust axonal growth and regenerative capacities of young neurons decrease substantially with age. This developmental downregulation of axonal growth may facilitate axonal pruning and neural circuit formation but limits functional recovery following nerve damage. While external factors influencing axonal growth have been extensively investigated, relatively little is known about the intrinsic molecular changes underlying the age-dependent reduction in regeneration capacity. We report that developmental downregulation of LIS1 is responsible for the decreased axonal extension capacity of mature dorsal root ganglion (DRG) neurons. In contrast, exogenous LIS1 expression or endogenous LIS1 augmentation by calpain inhibition restored axonal extension capacity in mature DRG neurons and facilitated regeneration of the damaged sciatic nerve. The insulator protein CTCF suppressed LIS1 expression in mature DRG neurons, and this reduction resulted in excessive accumulation of phosphoactivated GSK-3β at the axon tip, causing failure of the axonal extension. Conversely, sustained LIS1 expression inhibited developmental axon pruning in the mammillary body. Thus, LIS1 regulation may coordinate the balance between axonal growth and pruning during maturation of neuronal circuits.

© 2017. Published by The Company of Biologists Ltd.

Keywords: Axonal extension; Axonal transport; LIS1; Nerve degeneration; Nerve regeneration; Pruning

Conflict of interest statement

Competing interestsThe authors declare no competing or financial interests.

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