# Mechanisms of Hydra Development and Regeneration

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2024 · $536,251

## Abstract

PROJECT SUMMARY
Diverse animals can regenerate appendages and organs, or even their entire bodies, but the gene regulatory
networks underlying regeneration remain largely unknown because most of the commonly used research
organisms have limited regenerative capacity. However, technological advances are now enabling sophisticated
gene regulation studies in highly regnerative animals. To reveal the regulatory events that drive regeneration,
we use the small freshwater cnidarian Hydra, which has several advantages including: (1) The ability to
rapidly regenerate its whole body, including the nervous system, in two days, (2) Transgenesis and gene
knockdown approaches are well established, and (3) Hydra has a simple cellular composition consisting of ~25
cell types, allowing my research group to leverage transcriptomic and genomic approaches to study gene
regulation at the organismal level. In the previous funding period, we built a chromosome-scale assembly of
the Hydra genome with gene annotations and defined the cis-regulatory elements (CREs) genome wide. In
addition, we built a cell-type expression atlas of the whole animal, including a spatial and molecular map of the
Hydra nervous system. These resources enabled us to identify the transcription factors and CREs involved in
the specification of all Hydra cell types. Towards understanding how these specification pathways are activated
by injury during regeneration, we transcriptionally profiled the early stages of regeneration and discovered an
injury-induced activation of the Wnt-signaling pathway, which directs Hydra head morphogenesis. Our future
work will focus on two research themes. (1) We are defining the regulatory mechanisms that connect the
general injury response to the morphogenesis of new structures. The molecular response to injury is
conserved in animals regardless of their regenerative abilities. Therefore, it is critical to understand the GRNs
that connect the injury response to the activation of developmental pathways (e.g., the Wnt signaling pathway)
in regenerative animals, so that we can ultimately understand why these connections are not made in humans.
Furthermore, we aim to discover how regeneration GRNs drive the morphogenesis of new structures. (2) We
are leveraging the unique biology of Hydra to understand the regulatory mechanisms directing nervous
system regeneration. Adult stem cells in Hydra support the replacement of all neurons in an uninjured animal
every twenty days and allow Hydra to regenerate its entire nervous system after catastrophic injury to restore
behaviors in two days. Our goal is to uncover the neuronal specification pathways under homeostatic conditions,
and then determine how these pathways are activated during regeneration. Ultimately, we aim to connect the
injury induced GRN (defined in theme #1) to the activation of neurogenesis. The long-term goal of our
laboratory is to obtain a comprehensive mechanistic understanding of whole animal regenerati...

## Key facts

- **NIH application ID:** 10841248
- **Project number:** 2R35GM133689-06
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Celina Juliano
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $536,251
- **Award type:** 2
- **Project period:** 2019-09-01 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10841248

## Citation

> US National Institutes of Health, RePORTER application 10841248, Mechanisms of Hydra Development and Regeneration (2R35GM133689-06). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10841248. Licensed CC0.

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