Terminal differentiation precedes functional circuit integration in the peduncle neurons in regenerating Hydra vulgaris.

Understanding how neural circuits are regenerated following injury is a fundamental question in neuroscience. Hydra is a powerful model for studying this process because it has a simple neural circuit structure, significant and reproducible regenerative abilities, and established methods for creating transgenics with cell-type-specific expression. While Hydra is a long-standing model for regeneration and development, little is known about how neural activity and behavior is restored following significant injury.

Differentiation trajectories of the nervous system reveal transcriptional regulators of neuronal fate.

The small freshwater cnidarian polyp uses adult stem cells (interstitial stem cells) to continually replace neurons throughout its life. This feature, combined with the ability to image the entire nervous system (Badhiwala et al., 2021; Dupre & Yuste, 2017) and availability of gene knockdown techniques (Juliano, Reich, et al.

A chromosome-scale epigenetic map of the genome reveals conserved regulators of cell state.

The epithelial and interstitial stem cells of the freshwater polyp are the best-characterized stem cell systems in any cnidarian, providing valuable insight into cell type evolution and the origin of stemness in animals. However, little is known about the transcriptional regulatory mechanisms that determine how these stem cells are maintained and how they give rise to their diverse differentiated progeny. To address such questions, a thorough understanding of transcriptional regulation in is needed.

Multiple neuronal networks coordinate mechanosensory behavior.

is an emerging model organism for neuroscience due to its small size, transparency, genetic tractability, and regenerative nervous system; however, fundamental properties of its sensorimotor behaviors remain unknown. Here, we use microfluidic devices combined with fluorescent calcium imaging and surgical resectioning to study how the diffuse nervous system coordinates 's mechanosensory response. Mechanical stimuli cause animals to contract, and we find this response relies on at least two distinct networks of neurons in the oral and aboral regions of the animal.

Stem cell differentiation trajectories in resolved at single-cell resolution.

The adult polyp continually renews all of its cells using three separate stem cell populations, but the genetic pathways enabling this homeostatic tissue maintenance are not well understood. We sequenced 24,985 single-cell transcriptomes and identified the molecular signatures of a broad spectrum of cell states, from stem cells to terminally differentiated cells. We constructed differentiation trajectories for each cell lineage and identified gene modules and putative regulators expressed along these trajectories, thus creating a comprehensive molecular map of all developmental lineages in the adult animal.