Identification of a cell population functioning during repair processes of notochord injury

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

Lopez-Baez, J.C., Simpson, D.J., Forero, L.L., Zeng, Z., Brunsdon, H., Salzano, A., Brombin, A., Wyatt, C., Rybski, W., Huitema, L.FA., Dale, R.M., Kawakami, K., Englert, C., Chandra, T., Schulte-Merker, S., Hastie, N.D., and Patton, E.E.

eLife 2018;7:e30657 DOI:10.7554/eLife.30657

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.


Figure: In transgenic fish expressing GFP in the notochord vacuolated cells, GFP-expressing cells appeared 24-72 hours after injury.

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