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

Abstract

Regenerative therapy for degenerative spine disorders requires the identification of cells that can slow down and possibly reverse degenerative processes. Here, we identify a novel and unanticipated wound-specific notochord sheath cell subpopulation that expresses Wilms Tumor (WT) 1b following injury. Using live imaging in zebrafish, we show that localized damage leads to Wt1b expression in the sheath, and that wt1b+ cells migrate into the wound to form a stopper-like structure, likely to maintain structural integrity. At the wound wt1b+ and entpd5+ cells constitute distinct subpopulations, and mark the site of an extra vertebra that forms in an untypical manner via a cartilage intermediate. Surprisingly, wt1b+ cells become closely associated with the chordacentra and sustain wt1b expression for over 35 days during vertebra formation. Given that remnants of notochord cells remain in the adult intervertebral disc, the identification of novel subpopulations may have important implications for regenerative treatments for spine disorders.\n\nHighlightsO_LINotochord injury triggers wound-specific expression of wt1b in novel sheath subpopulation\nC_LIO_LIWT1b notochord sheath cells fill injury site and form stopper-like structure\nC_LIO_LIWT1b subpopulation marks site of a new vertebra that forms via a cartilage intermediate\nC_LIO_LIWT1b wound-specific subpopulation perdures throughout and after vertebra repair\nC_LI