Wnt–β-catenin signaling promotes zebrafish osteoblast dedifferentiation by wnt10a-mediated inhibition of NF-κB

ABSTRACT: Dedifferentiation of mature cells is a key mechanism for generating source cells in many regenerative systems, including the zebrafish fin. Here we show that osteoblast injury responses involve rapid and extensive transcriptional reprogramming, yielding a cell state that closely resembles embryonic osteoblasts while also activating regeneration-specific genes. Among these, wnt10a is the only canonical Wnt ligand induced specifically in osteoblasts during early phases after amputation. Using genetic perturbations, we demonstrate that Wnt10a-dependent Wnt/β-catenin signaling is essential for osteoblast dedifferentiation and acts cell-autonomously to drive this process. Loss of wnt10a or Wnt/β-catenin activity blocks the dedifferentiation program, whereas wnt10a overexpression enhances dedifferentiation and is sufficient to induce it even without injury. Wnt/β-catenin signaling promotes dedifferentiation by suppressing NF-κB activity, placing it upstream of known inhibitory cues. Notably, wnt10a also stimulates cardiomyocyte dedifferentiation, revealing a conserved role in activating source-cell formation during regeneration.

ORGANISM(S): Danio rerio

PROVIDER: GSE312516 | GEO | 2026/10/01

REPOSITORIES: GEO