Journal
NATURE COMMUNICATIONS
Volume 8, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-017-00143-0
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Funding
- Deutsche Forschungsgemeinschaft (Forschungsstipendium) [WE5736/1-1]
- BBSRC [BB/L021498/1]
- NC3Rs [NC/l001063/1]
- Biotechnology and Biological Sciences Research Council [BB/L021498/1] Funding Source: researchfish
- National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) [NC/L001063/1] Funding Source: researchfish
- BBSRC [BB/L021498/1] Funding Source: UKRI
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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/beta-catenin pathway in fibroblast-like cells in the lesion site is pivotal for axon re-growth and functional recovery. Wnt/beta-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/beta-catenin pathway inhibition and is sufficient to accelerate regeneration. We demonstrate that in a vertebrate of high regenerative capacity, Wnt/beta-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/beta-catenin pathway and Collagen XII may be targets for extracellular matrix manipulations in non-regenerating species.
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