Transcriptomics of Neural Regeneration in Echinoderms: A Roadmap for Future Research

Because of the lack of the intrinsic regenerative capacity, the injured central nervous system (CNS) in humans does not restore the severed neural connections. Therefore, the respective body functions in affected patients never fully recover. There are animals, however, who can readily regenerate even severe damage to major parts of their CNS. Echinoderms, a phylum of marine invertebrates, have emerged as very promising model organisms in regenerative biology. Their phylogenetic position among basal deuterostomes makes them particularly valuable for understanding the evolution of neural regeneration and also as an important source of insights into how to improve regeneration in human patients. As the first step in characterizing the gamut of molecular processes underlying efficient neural regeneration in echinoderms, we carried out a high-throughput analysis of transcriptomic changes in the regenerating radial nerve cord in the sea cucumber Holothuria glaberrima. Functional analysis of differentially expressed genes suggested a key role of the extracellular matrix remodeling and identified suppression of the glutamate excitotoxicity pathway as one of the possible adaptations contributing to the efficiency of neural regeneration. Analysis of expression of pluripotency factors showed that, surprisingly, most of them remained expressed at the constant level both in the normal and regenerating tissue. Only Myc, the echinoderm homolog of the mammalian c-Myc, was highly up-regulated during regeneration. Functional analysis suggests that during the early regeneration phase, this transcription factor is required for proper dedifferentiation of glial cells and for initiation of the programmed cell death in the vicinity of the injury.