DECODING PRINCIPLES OF REGENERATIVE NEUROGENESIS FOR CENTRAL NERVOUS SYSTEM REGENERATION

Regeneration of the central nervous system (CNS) is limited in various animal groups. Understanding how regenerative species overcome such constraints enables mechanistic breakthroughs. The marine annelid Platynereis dumerilii is a powerful invertebrate regeneration model uniquely suited for this challenge: It possesses a molecular switch that controls regenerative competence, and a CNS with a deep evolutionary connection to vertebrates that can morphologically and functionally regenerate within days following posterior amputation.
Recent research in our lab has successfully pioneered a single-cell RNA sequencing approach to provide a comprehensive landscape of cell populations in the trunk and their regenerative response. This work revealed that new stem cells for CNS regeneration likely arise from dedifferentiation of epidermal tissue (Stockringer & Adelmann et al., 2024). Taking advantage of this unique platform, we are extending the analysis into neurogenic stages, aiming to (i) define the spatiotemporal dynamics of neural induction and (ii) to elucidate how functional integration arises.
Using single-cell transcriptomics, we have mapped candidate progenitor populations and predicted lineage relationships to their progeny. We are using these data to identify gene regulatory networks underlying the respective transitions.
Complementing this cell type-centric approach, we develop behavioural assays for functional locomotion readouts. We intend to use these assays to precisely map the fate of newly arising neurons as well as their connectivity to the existing circuitry.
Together, our research establishes mechanistic principles underlying regenerative neurogenesis, the subsequent integration, and identifies what distinguishes regenerative success from failure – a question with implications across the breadth of the animal kingdom.