Species within nearly all extant animal lineages are capable of regenerating body parts. However, it remains unclear whether the gene expression programme controlling regeneration is evolutionarily conserved. Brittle stars are a species-rich class of echinoderms with outstanding regenerative abilities, but investigations into the genetic bases of regeneration in this group have been hindered by the limited available genomic resources. Here, we report a chromosome-scale genome assembly for the brittle star Amphiura filiformis. We show that the brittle star displays the most rearranged genome amongst echinoderms sequenced to date, featuring a reorganised Hox cluster reminiscent of the rearrangements observed in sea urchins. In addition, we performed an extensive profiling of gene expression throughout brittle star adult arm regeneration and identified sequential waves of gene expression governing wound healing, proliferation and differentiation. We conducted comparative transcriptomic analyses with other invertebrate and vertebrate models for appendage regeneration and uncovered hundreds of genes with conserved expression dynamics, notably during the proliferative phase of regeneration. Our findings emphasise the crucial importance of echinoderms to detect long-range expression conservation between vertebrates and classical invertebrate regeneration model systems. Overall design: RNA-seq samples of brittle star arm regeneration timecoure (8 samples) and explant experiments to compare regeneration and wound healing