Wilms Tumor 1b defines a wound-specific sheath cell subpopulation associated with notochord repair
- University of Edinburgh, United Kingdom
- Hubrecht Institute, Netherlands
- Loyola University Chicago Quinlan, United States
- National Institute of Genetics, Japan
- Leibniz Institute for Age Research-Fritz Lipmann Institute, Germany
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 vertebra, which forms 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.
Article and author information
Author details
Stefan Schulte-Merker
E Elizabeth Patton
Funding
Medical Research Council University Unit Award to the University of Edinburgh for the MRC Human Genetics Unit (U127527202)
- Juan Carlos Lopez-Baez
- Zhiqiang Zeng
- Alessandro Brombin
- Witold Rybski
- Nicholas D Hastie
- E Elizabeth Patton
Japan Society for the Promotion of Science (15H02370)
- Koichi Kawakami
Japan Agency for Medical Research and Development (National BioResource Project)
- Koichi Kawakami
H2020 European Research Council (ZF-MEL-CHEMBIO - 648489)
- Hannah Brunsdon
- Alessandro Brombin
- E Elizabeth Patton
Melanoma Research Alliance (401181)
- Alessandro Brombin
- E Elizabeth Patton
L'Oreal USA (401181)
- Alessandro Brombin
- E Elizabeth Patton
Cells in Motion - Cluster of Excellence
- Stefan Schulte-Merker
Leibniz-Gemeinschaft
- Christoph Englert
Medical Research Council (Discovery Award MC_PC_15075)
- Angela Salzano
University Of Edinburgh (Chancellor's Fellowship)
- Tamir Chandra
Medical Research Council (Doctoral Training Programme in Percision Medicine)
- Daniel J Simpson
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All work presented in this study has been performed in accordance with the UK legal requirements for the protection of animals used for experimental or other scientific research under the Animal (Scientific Procedures) Act 1986. All experiments were approved by the University of Edinburgh Ethics Committee, and performed under the Home Office Project License 70/800 to EEP. Zebrafish welfare and husbandry were closely monitored by the MRC Human Genetics Unit Zebrafish Facility staff.
Copyright
© 2018, Lopez-Baez et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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