# Cellular and Molecular Mechanisms of Murine Digit Regeneration

> **NIH NIH F32** · WASHINGTON UNIVERSITY · 2020 · $60,080

## Abstract

Project Summary
 Humans have limited regenerative potential after extensive musculoskeletal injuries, particularly
following limb loss. As such, the ability to biologically restore the missing limb will significantly improve the
quality of life for millions of amputees. To understand the fundamental mechanisms guiding regeneration of
complex musculoskeletal tissues or organs, mouse models of digit amputation have been used to study
musculoskeletal regrowth, which occurs in a spatiotemporally controlled manner upon distal digit tip removal.
While much progress has been made to elucidate the cell types and growth factors responsible for this natural
regenerative response, the exact cellular and molecular mechanisms underlying digit regeneration have yet to
be revealed. Recent studies suggest that cells derived from the periosteum participate in bone regrowth in
adults, and thus represent a possible source of osteoblast lineage cells. However, it remains unknown to what
extent this specific cell population plays a direct role in digit regeneration.
 We hypothesize that spatiotemporal activation of distinct molecular events after distal digit amputation
mediates the activation, proliferation, and/or differentiation of periosteal cells (PCs). To test this hypothesis, we
will investigate the spatiotemporal response of PCs after digit amputation using Osx-CreERT2;Ai9 inducible
reporter transgenic mice in Aim 1, which will permit lineage tracing of this cell population. Furthermore, we will
test the requirement of proliferating PCs during digit regeneration by inducible conditional ablation of replicating
PCs using 3.6Col1a1-tk transgenic mice. Finally, we will determine the signaling cues that activate and sustain
digit regeneration in Aim 2 using RNA in situ hybridization and tissue-specific RNA-sequencing, with a specific
focus on the spatiotemporal distribution of canonical Wnt signaling. By identifying the cells and molecular
pathways vital to regeneration, this proposal will open new avenues to therapies that will help restore the
biological composition and structure of the lost tissues.

## Key facts

- **NIH application ID:** 9889795
- **Project number:** 5F32AR074895-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Feini Qu
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $60,080
- **Award type:** 5
- **Project period:** 2019-02-01 → 2020-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9889795

## Citation

> US National Institutes of Health, RePORTER application 9889795, Cellular and Molecular Mechanisms of Murine Digit Regeneration (5F32AR074895-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9889795. Licensed CC0.

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