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Wnt signaling controls pro-regenerative Collagen XII in functional spinal cord regeneration in zebrafish

Author

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  • Daniel Wehner

    (University of Edinburgh)

  • Themistoklis M. Tsarouchas

    (University of Edinburgh)

  • Andria Michael

    (University of Edinburgh)

  • Christa Haase

    (TechnischeUniversität Dresden)

  • Gilbert Weidinger

    (Ulm University)

  • Michell M. Reimer

    (Technische Universität Dresden, DFG-Center of Regenerative Therapies Dresden, Cluster of Excellence at the TU Dresden)

  • Thomas Becker

    (University of Edinburgh)

  • Catherina G. Becker

    (University of Edinburgh)

Abstract

The inhibitory extracellular matrix in a spinal lesion site is a major impediment to axonal regeneration in mammals. In contrast, the extracellular matrix in zebrafish allows substantial axon re-growth, leading to recovery of movement. However, little is known about regulation and composition of the growth-promoting extracellular matrix. Here we demonstrate that activity of the Wnt/β-catenin pathway in fibroblast-like cells in the lesion site is pivotal for axon re-growth and functional recovery. Wnt/β-catenin signaling induces expression of col12a1a/b and deposition of Collagen XII, which is necessary for axons to actively navigate the non-neural lesion site environment. Overexpression of col12a1a rescues the effects of Wnt/β-catenin pathway inhibition and is sufficient to accelerate regeneration. We demonstrate that in a vertebrate of high regenerative capacity, Wnt/β-catenin signaling controls the composition of the lesion site extracellular matrix and we identify Collagen XII as a promoter of axonal regeneration. These findings imply that the Wnt/β-catenin pathway and Collagen XII may be targets for extracellular matrix manipulations in non-regenerating species.

Suggested Citation

  • Daniel Wehner & Themistoklis M. Tsarouchas & Andria Michael & Christa Haase & Gilbert Weidinger & Michell M. Reimer & Thomas Becker & Catherina G. Becker, 2017. "Wnt signaling controls pro-regenerative Collagen XII in functional spinal cord regeneration in zebrafish," Nature Communications, Nature, vol. 8(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00143-0
    DOI: 10.1038/s41467-017-00143-0
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    Cited by:

    1. Valentina Cigliola & Adam Shoffner & Nutishia Lee & Jianhong Ou & Trevor J. Gonzalez & Jiaul Hoque & Clayton J. Becker & Yanchao Han & Grace Shen & Timothy D. Faw & Muhammad M. Abd-El-Barr & Shyni Var, 2023. "Spinal cord repair is modulated by the neurogenic factor Hb-egf under direction of a regeneration-associated enhancer," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Yu Xia & Sierra Duca & Björn Perder & Friederike Dündar & Paul Zumbo & Miaoyan Qiu & Jun Yao & Yingxi Cao & Michael R. M. Harrison & Lior Zangi & Doron Betel & Jingli Cao, 2022. "Activation of a transient progenitor state in the epicardium is required for zebrafish heart regeneration," Nature Communications, Nature, vol. 13(1), pages 1-18, December.

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