Adult Acomys DRG explants exhibit a radially organized neurite architecture distinct from Mus explants

Abstract

The African spiny mouse, Acomys cahirinus, is an unusual mammalian model of regeneration that exhibits reduced fibrotic repair compared with Mus musculus. To determine whether this species-level difference is reflected in neural explant architecture, we compared adult dorsal root ganglion (DRG) explants from Acomys and Mus under identical in vitro conditions. Instead of focusing solely on neurite length, we examined the spatial organization of the outgrowth field and its relationship to non-neuronal cellular architecture over time in culture. Both species exhibited neurite extension; however, their outgrowth patterns differed markedly. Acomys explants frequently developed a compact, radially organized scaffold-like phenotype characterized by aligned vimentin-positive structures and coordinated neurite extension, whereas Mus explants more commonly displayed a dispersed, sheet-like morphology with reduced neurite alignment. Importantly, neurite growth in Mus was not absent, but was spatially restricted and largely retained in the central, more three-dimensional region of the explant. Temporal analysis showed that the organized phenotype emerged progressively in Acomys but was not observed in Mus. While the organized phenotype was associated with increased neurite length, this effect was specific to the phenotype and did not fully account for the architectural divergence between species. Together, these findings indicate that a key species difference lies in the organization of neurite outgrowth and associated non-neuronal structure rather than in neurite extension alone. This study identifies explant architecture as a relevant readout of species-specific regenerative biology and suggests that non-neuronal microenvironmental organization may contribute to regeneration-permissive growth states.