# Motility and Guidance Signals Control Migration of Muscle Precursors

> **NIH NIH P20** · UNIVERSITY OF MAINE ORONO · 2024 · $268,120

## Abstract

Jared Talbot Project summary:
Cell migrations are vital to generating a patterned musculature, but only a few of the cues that
activate the cell’s motility are known and it remains unclear how muscle progenitors decide to
move towards one destination versus another. Here, we will investigate the cues that activate
muscle precursor cell motility (Aim 1) and guide the migrating cells (Aim 2) using zebrafish
embryos as a model system. In vertebrate embryos, muscle precursor cell migration begins with
an epithelial-to-mesenchymal transition (EMT); the cells are then actively guided from somites
to new locations in the body, migrating as mesenchymal cell-streams. In mammalian embryos,
these cell streams originate from several axial levels to generate over 100 muscles in many
body regions. In zebrafish embryos, the homologous migrations are simpler, producing only four
muscles: the two limb muscles, the sole neck muscle, and the chest muscle. Paired with other
zebrafish strengths, this simplicity makes the zebrafish embryo an excellent model system for
understanding muscle precursor cell migrations. We have developed transgenic and mutant
lines that enable us to investigate muscle precursor migration in zebrafish embryos. Using these
tools, we recently demonstrated that the transcription factors six1 and six4 (collectively termed
“six1/4”) are essential for muscle precursor migration in zebrafish. In six1/4 mutants, the muscle
precursors fail to undergo EMT and fail to activate the migration-promoting gene met, which
encodes a metastasis-inducing receptor protein. Although the six1/4 mutants completely lack
precursor migration, this process is only delayed in zebrafish met mutants, suggesting that
six1/4 targets additional genes that stimulate motility. In Aim 1A, we will use an unbiased
chemical screen to identify new molecules that stimulate muscle precursor motility and
guidance. In Aim 1B, we investigate one pathway already suggested by this screen to influence
EMT during this migration. In Aim 2, we will investigate how chemokine signals influence this
migration. Muscle precursors are thought to be attracted by chemokine (Cxcl12) signaling,
which is received by the receptor Cxcr4 and antagonized by the scavenging receptor Ackr3; we
propose that the interplay of these two receptors imparts directionality to muscle precursor
migration. Chemokine signaling will be altered using genetic mutants and chemical modulators.
Cell movement will be analyzed using 3D cell tracking in transgenic embryos. Together these
experiments will provide insights into the initiation and guidance of muscle precursor cells, with
potential application in other migration-dependent processes like muscle regeneration and
metastasis.

## Key facts

- **NIH application ID:** 10821306
- **Project number:** 5P20GM144265-02
- **Recipient organization:** UNIVERSITY OF MAINE ORONO
- **Principal Investigator:** Jared Coffin Talbot
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $268,120
- **Award type:** 5
- **Project period:** 2023-04-05 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10821306

## Citation

> US National Institutes of Health, RePORTER application 10821306, Motility and Guidance Signals Control Migration of Muscle Precursors (5P20GM144265-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10821306. Licensed CC0.

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