# Regulation of Appendage Regeneration in Zebrafish

> **NIH NIH R01** · DUKE UNIVERSITY · 2022 · $382,059

## Abstract

Adult teleost fish and urodele amphibians can regenerate entire amputated appendages. By contrast,
regenerative healing of adult mammalian limbs is limited to the very tips of digits. One of the key challenges in
developmental biology is to understand how and why tissue regeneration occurs. The hallmark of limb or fin
regeneration is formation of a blastema, a mesenchymal structure that contains progenitor cells for new skeletal
elements. As regeneration proceeds, blastemal cell proliferation and patterning are regulated such that lost
tissues of correct size and shape are replaced. While the catalogue of defined cell dynamics and molecular
factors in tissue regeneration is expanding, we know much less of how genes involved in regenerative events
are engaged upon injury. That is, what are the DNA sequences that recruit activators (or repressors) of gene
programs during tissue regeneration, how are these sequences distributed throughout the genomes of
regeneration-competent animals, and what are the transcription factors that engage with these sequences?
Recently, we identified a class of distal gene regulatory elements that preferentially activate gene expression
during regeneration, can be engineered in simple constructs to express developmental factors that promote
regeneration, and have the potential to be recognized by the transcriptional machinery of distant species. The
overall goal of this proposal is to discover gene regulatory concepts and mechanisms that restore size and
pattern to an amputated appendage. We will test the hypothesis that enhancer and silencer elements are crucial
regulatory modules enabling appendage regeneration in zebrafish. This work will increase understanding of
developmental regulation during vertebrate tissue regeneration, and provide important perspective for
comprehending, and perhaps changing, the existing limitations in regenerative capacity of human tissues.

## Key facts

- **NIH application ID:** 10428599
- **Project number:** 5R01HD105033-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** KENNETH D POSS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $382,059
- **Award type:** 5
- **Project period:** 2021-06-15 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10428599

## Citation

> US National Institutes of Health, RePORTER application 10428599, Regulation of Appendage Regeneration in Zebrafish (5R01HD105033-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10428599. Licensed CC0.

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