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Elife. 2018 Feb 6;7. pii: e30657. doi: 10.7554/eLife.30657.

Wilms Tumor 1b defines a wound-specific sheath cell subpopulation associated with notochord repair.

Author information

1
MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
2
CRUK Edinburgh Centre, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
3
Hubrecht Institute - KNAW & UMC Utrecht, Utrecht, Netherlands.
4
Faculty of Medicine, Institute for Cardiovascular Organogenesis and Regeneration, WWU Münster, Münster, Germany.
5
CiM Cluster of Excellence, Münster, Germany.
6
Department of Biology, Loyola University Chicago, Chicago, United States.
7
Division of Molecular and Developmental Biology, National Institute of Genetics, Mishima, Japan.
8
Department of Molecular Genetics, Leibniz Institute for Age Research-Fritz Lipmann Institute, Jena, Germany.
9
Institute of Biochemistry and Biophysics, Friedrich-Schiller-University, Jena, Germany.
#
Contributed equally

Abstract

Regenerative therapy for degenerative spine disorders requires the identification of cells that can slow down and possibly reverse degenerative processes. Here, we identify an unanticipated wound-specific notochord sheath cell subpopulation that expresses Wilms Tumor (WT) 1b following injury in zebrafish. We show that localized damage leads to Wt1b expression in sheath cells, and that wt1b+cells migrate into the wound to form a stopper-like structure, likely to maintain structural integrity. Wt1b+sheath cells are distinct in expressing cartilage and vacuolar genes, and in repressing a Wt1b-p53 transcriptional programme. At the wound, wt1b+and entpd5+ cells constitute separate, tightly-associated subpopulations. Surprisingly, wt1b expression at the site of injury is maintained even into adult stages in developing vertebrae, which form in an untypical manner via a cartilage intermediate. Given that notochord cells are retained in adult intervertebral discs, the identification of novel subpopulations may have important implications for regenerative spine disorder treatments.

KEYWORDS:

Wilms Tumor 1; developmental biology; heterogeneity; notochord; sheath cells; stem cells; vertebrae; wound healing; zebrafish

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