RRC ID |
51249
|
著者 |
Wehner D, Tsarouchas TM, Michael A, Haase C, Weidinger G, Reimer MM, Becker T, Becker CG.
|
タイトル |
Wnt signaling controls pro-regenerative Collagen XII in functional spinal cord regeneration in zebrafish.
|
ジャーナル |
Nat Commun
|
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.Following spinal injury in zebrafish, non-neural cells establish an extracellular matrix to promote axon re-growth but how this is regulated is unclear. Here, the authors show that Wnt/β-catenin signaling in fibroblast-like cells at a lesion activates axon re-growth via deposition of Collagen XII.
|
巻・号 |
8(1)
|
ページ |
126
|
公開日 |
2017-7-25
|
DOI |
10.1038/s41467-017-00143-0
|
PII |
10.1038/s41467-017-00143-0
|
PMID |
28743881
|
PMC |
PMC5526933
|
MeSH |
Animals
Animals, Genetically Modified
Axons / metabolism
Collagen Type XII / genetics
Collagen Type XII / metabolism*
Larva / genetics
Larva / metabolism
Larva / physiology
Microscopy, Confocal
Recovery of Function
Spinal Cord Injuries / genetics
Spinal Cord Injuries / metabolism
Spinal Cord Injuries / physiopathology
Spinal Cord Regeneration*
Time-Lapse Imaging / methods
Wnt Signaling Pathway*
Zebrafish / genetics
Zebrafish / metabolism
Zebrafish / physiology
Zebrafish Proteins / genetics
Zebrafish Proteins / metabolism*
beta Catenin / metabolism
|
IF |
12.121
|
引用数 |
37
|
リソース情報 |
ゼブラフィッシュ |
Tg(6xTcf/LefBS-miniP:d2EGFP) |