# Defining mechanistic differences between embryonic and regenerative organogenesis

> **NIH NIH F32** · STOWERS INSTITUTE FOR MEDICAL RESEARCH · 2021 · $17,615

## Abstract

RESEARCH SUMMARY
Adult tissue regeneration shares key genetic requirements with embryonic development. However, despite
intense interest from the field of regenerative medicine, the natural mechanisms that allow for the controlled use
of embryonic factors to construct functional tissue and organs de novo in adults remains poorly understood. This
proposal focuses on the pharynx of the starlet sea anemone Nematostella vectensis as a simple and genetically
powerful model system to elucidate the mechanistic similarities and differences between developmental and
regenerative organ formation. The Nematostella pharynx is uniquely suited to address this question as it is
formed through gastrulation during embryonic development and the functional organ is capable of being
regenerated in its entirety following complete removal in the adult. In preliminary experiments, I have identified
forkhead box A (foxA), an evolutionarily conserved transcription factor, as expressed in both pharynx
development and regeneration. Additionally, through functional genetic analysis I have shown a requirement for
foxA in pharynx formation during embryogenesis. This research proposal aims to 1) determine the precise role
of foxA in pharyngeal cell determination in a regenerative organism, 2) define the foxA-dependent transcriptional
program required for embryonic pharynx formation, and 3) elucidate a regeneration-specific pharyngeal growth
program directed by foxA. Functional genetic experiments using transgenic adult animal lines, systemic RNAi,
and mosaic gene expression will assess the role of foxA in pharynx development and regeneration. Additionally,
RNA sequencing (RNAseq) and chromatin immunoprecipitation DNA sequencing (ChIPseq) analyses will
determine embryogenesis-specific and regeneration-specific foxA gene targets and binding sites. These foxA-
dependent genes and regulatory binding sites will be further interrogated through genetic perturbation using
systemic RNAi and CRISPR-mediated genome editing to mechanistically compare embryonic and post-
embryonic organogenesis programs in the same animal. Studies aimed at understanding the similarities and
differences of complex organ formation through development and regeneration will reveal deep insight into the
natural mechanisms that underlie whole-organ regeneration and could provide conceptual insights to guide the
development of future regenerative therapeutics.
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## Key facts

- **NIH application ID:** 10396153
- **Project number:** 3F32GM131522-02S1
- **Recipient organization:** STOWERS INSTITUTE FOR MEDICAL RESEARCH
- **Principal Investigator:** Eric Michael Hill
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $17,615
- **Award type:** 3
- **Project period:** 2019-08-01 → 2021-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10396153

## Citation

> US National Institutes of Health, RePORTER application 10396153, Defining mechanistic differences between embryonic and regenerative organogenesis (3F32GM131522-02S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10396153. Licensed CC0.

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