# Ion signaling and cell state transitions for organ size control of regenerating zebrafish fins

> **NIH NIH F31** · UNIVERSITY OF OREGON · 2022 · $45,181

## Abstract

PROJECT SUMMARY
This project provides the applicant with Ph.D. training intersecting cell, developmental and regenerative
biology. Zebrafish regenerate resected fins, including their bony ray skeletons, back to the original size
irrespective of injury extent. Yet, how fins “know” when to stop growing as the correct size is attained is poorly
understood. The applicant’s laboratory recently proposed a new model for robust fin size restoration based on
initial amount of a skeletal geometry-defined “niche” population and its progressive depletion by a cell state
transition. Further, the group found dramatic fin overgrowth in the classic zebrafish mutant longfint2 is caused
by cis-ectopic expression of the kcnh2a K+ channel. Kcnh2a in longfint2 results in niche cell perdurance and
therefore excessive outgrowth during regeneration. The applicant’s transplant experiments show ectopic
kcnh2a in the mesenchyme lineage that generates niche cells is sufficient for overgrowth. Yet, how kcnh2a
disrupts orderly niche depletion is unknown. Published studies show inhibiting the Ca2+-dependent
phosphatase calcineurin also causes striking fin overgrowth. The applicant’s new epistasis experiments
suggest Kcnh2a functions upstream of calcineurin. Their new transgenic Ca2+ reporter identifies dynamic Ca2+
levels in niche/mesenchyme cells that preliminary transcriptomics indicate depend on specifically expressed
Ca2+ channels. This leads to the central hypothesis that Ca2+ channel activity and dynamic Ca2+ levels activate
calcineurin signaling to promote niche-to-mesenchymal cell state transitions and end fin regrowth. The
applicant will pursue three specific aims: 1) Determine how Kcnh2a impacts intracellular Ca2+ dynamics during
fin regeneration, 2) Identify Ca2+ channels influencing regenerated fin size, and 3) Determine if calcineurin
promotes niche-to-mesenchymal cell state transitions to slow fin outgrowth. In parallel with thesis research, the
applicant will pursue extensive scientific communication training and activities, mentoring and teaching
experiences, professional development workshops and networking events, and a diversity-supporting
leadership role in the Women in Graduate Science organization.

## Key facts

- **NIH application ID:** 10402793
- **Project number:** 5F31HD103459-02
- **Recipient organization:** UNIVERSITY OF OREGON
- **Principal Investigator:** Heather K Le Bleu
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $45,181
- **Award type:** 5
- **Project period:** 2021-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10402793

## Citation

> US National Institutes of Health, RePORTER application 10402793, Ion signaling and cell state transitions for organ size control of regenerating zebrafish fins (5F31HD103459-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10402793. Licensed CC0.

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