# The function of chromatin remodeling in the patterning of the salamander limb

> **NIH NIH R15** · UNIVERSITY OF MASSACHUSETTS BOSTON · 2022 · $457,500

## Abstract

PROJECT SUMMARY:
 Nearly two million people in the United States are living with limb loss and the devastating effects that
this loss has on their quality of life and economic status. The long-term goal of this research is to make it possible
for these patients to regrow their extremities by inducing an endogenous regenerative response. Accomplishing
this goal will require the study of endogenous limb regeneration in animals that do this naturally, such as the
Mexican Axolotl. One essential question that has not been resolved is how the mature limb cells become capable
of making the pattern of the regenerated limb. Studies have shown that prior to the formation of new pattern, the
cells that contribute to the regenerate acquire positional plasticity that allows them to become reprogrammed by
patterning signals in the regenerating environment. Preliminary studies have identified that 1) a combination of
FGF and BMP signaling are sufficient to make the mature limb cells positionally plastic, and 2) that a significant
loss the inhibitory chromatin mark H3K27me3 occurs in limb cells when they acquire positional plasticity.
Members of both the FGF and BMP signaling cascades have been previously shown in other systems to interact
with chromatin modifying enzymes which can lead to the loss of H3K27me3 on specific genes. The central
hypothesis of this study is that BMP and FGF signaling are required for the chromatin modifications that make
limb cells capable of acquiring new pattern. To investigate how FGF and BMP signaling induce positional
plasticity a two-pronged approach will be employed. The experiments in Aim 1 will utilize H3K27me ChIP-seq
and RNA-seq to identify gene candidates that are directly downstream of BMP and FGF signaling and determine
whether these gene targets are mutually dependent on both BMP and FGF signaling. Aim 2 will employ FACS,
quantitative microscopy, and phenomenological assays to evaluate whether the mitogenic activity of FGF and
BMP is required for both the loss of H3K27me3 and the acquisition of positional plasticity.

## Key facts

- **NIH application ID:** 10359548
- **Project number:** 2R15HD092180-02
- **Recipient organization:** UNIVERSITY OF MASSACHUSETTS BOSTON
- **Principal Investigator:** CATHERINE D MCCUSKER
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $457,500
- **Award type:** 2
- **Project period:** 2018-09-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10359548

## Citation

> US National Institutes of Health, RePORTER application 10359548, The function of chromatin remodeling in the patterning of the salamander limb (2R15HD092180-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10359548. Licensed CC0.

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