A molecular, spatial and regulatory atlas of the Hydra vulgaris nervous system.

Hydra vulgaris, a cnidarian with a simple nerve net, is an emerging model for developmental, regenerative and functional neuroscience. Its genetic tractability and capacity for whole-system imaging make it well suited for studying neuron replacement, regeneration and neural circuit function. Here, we present the most comprehensive molecular and spatial characterization of the H. vulgaris nervous system to date. Using single-cell RNA sequencing, we identified eight neuron types, each defined by distinct neuropeptide expression, and further resolved these into 15 transcriptionally distinct subtypes with unique spatial distributions and morphologies. These data enabled a detailed examination of the molecular components of neuronal communication and excitability. To investigate the gene regulatory networks underlying neuronal differentiation, we applied trajectory inference, identified key transcription factors, and performed ATAC-seq on sorted neurons to map chromatin accessibility. All datasets are available through an interactive, user-friendly web portal to support broad use by the research community. Together, these resources provide a foundation for uncovering molecular mechanisms that govern nervous system development, homeostasis, regeneration and function in H. vulgaris.