Neurogenesis during Brittle Star Arm Regeneration Is Characterised by a Conserved Set of Key Developmental Genes

SIMPLE SUMMARY: Injuries to the central nervous system most often lead to irreversible damage in humans. Brittle stars are marine animals related to sea stars and sea urchins, and are one of our closest evolutionary relatives among invertebrates. Extraordinarily, they can perfectly regenerate their nerves even after completely severing the nerve cord after arm amputation. Understanding what genes and cellular mechanisms are used for this natural repair process in the brittle star might lead to new insights to guide strategies for therapeutics to improve outcomes for central nervous system injuries in humans. ABSTRACT: Neural regeneration is very limited in humans but extremely efficient in echinoderms. The brittle star Amphiura filiformis can regenerate both components of its central nervous system as well as the peripheral system, and understanding the molecular mechanisms underlying this ability is key for evolutionary comparisons not only within the echinoderm group, but also wider within deuterostomes. Here we characterise the neural regeneration of this brittle star using a combination of immunohistochemistry, in situ hybridization and Nanostring nCounter to determine the spatial and temporal expression of evolutionary conserved neural genes. We find that key genes crucial for the embryonic development of the nervous system in sea urchins and other animals are also expressed in the regenerating nervous system of the adult brittle star in a hierarchic and spatio-temporally restricted manner.