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

Daniel Wehner, Themistoklis M. Tsarouchas, Andria Michael, Christa Haase, Gilbert Weidinger, Michell M. Reimer, Thomas Becker () and Catherina G. Becker ()
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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

Nature Communications, 2017, vol. 8, issue 1, 1-17

Abstract: 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.

Date: 2017
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DOI: 10.1038/s41467-017-00143-0

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