UC Davis

The number of research organisms used to study nervous system development and function has substantially increased in recent years due to advances in technology, such as single cell RNA sequencing. This has enabled researchers to characterize the neuronal transcriptional diversity in a wide range of organisms. However, very few comprehensive transcriptional descriptions of adult nervous systems currently exist. Here, we provide a transcriptional analysis of the entire Hydra vulgaris adult nervous system. Although Hydra shares many of the same experimental advantages as well-established invertebrate models, such as small size, optical transparency, and ability to test gene function, it is also able to regenerate its entire nervous system from adult stem cells. This makes Hydra an excellent model for studying nervous system development and regeneration at the whole-organism level.

Although Hydra has been studied for over 300 years, the Hydra nervous system has never been fully defined on a molecular level. Prior to this work, the diversity, transcriptional profiles, and developmental lineages of Hydra neurons were unknown. In this dissertation, I present an extensive set of resources characterizing the homeostatic Hydra nervous system. Chapter 1 describes the generation of a whole-animal single-cell RNA-seq atlas for Hydra vulgaris. This includes the first molecular map of the Hydra nervous system, identification of 11 transcriptionally distinct neuronal subtypes, and first validated molecular markers for endodermal neuronal subtypes. Chapter 2 presents the most comprehensive transcriptional characterization of the adult Hydra nervous system to date. This includes both differentiation and transdifferentiation pathways and the identification of the chromatin states of Hydra’s 11 neuronal subtypes. The appendix includes additional manuscripts that were collaborative efforts stemming from my thesis work.