Polycomb Repressive Complex 2 Ensures Robust Skeletal Growth and Patterning During Zebrafish Fin Regeneration

Presenter(s): Bryson Tyler Ricamona—Biology

Faculty Mentor(s): Scott Stewart, Kryn Stankunas

Session 5: The Bonds that Make Us

After amputation zebrafish regenerate their fins back to the correct size and shape . Fin bone regeneration is driven by an endogenous “stem cell” population generated by dedifferentiation of mature osteoblasts at the amputation site . The resulting osteo-progenitors both self-renew and re-differentiate until regeneration is complete . Yet it is unknown how mature osteoblasts reprogram and change gene expression patterns upon dedifferentiation . Recent in mammal work links chromatin function and covalent modification of histones to cellular potency and differentiation . Ezh1 and Ezh2 are key subunits of Polycomb Repressive Complex 2 (PRC2) that tri-methylates lysine 27 of histone H3 (H3K27me3) to maintain repressed states of developmental regulatory genes in mammals . To test if PRC2 is required for dedifferentiation during fin regeneration we analyzed regeneration in ezh1 and ezh2 mutant zebrafish . Here we show that, although ezh1-/-; ezh2+/- mutant fins regenerated largely to the same size as wildtype, they display notable defects in bone patterning . These defects, including the formation of large bony plates and the fusion of adjacent rays occur within 5 days post-amputation suggesting PRC2 is needed for a relatively early phase of regeneration . Such defects are exacerbated when PRC2 mutants are subjected to a second round of amputation in the regenerated region, possibly due to an increased amount of cells with abnormal H3K27me3 levels leading to dysregulation of gene expression . This suggests that PRC2 is a necessary regulator in the lineage specific osteoblast pathway during regeneration due to observations of abnormal bony ray morphology .

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