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Regulation of Muscle Stem Cell Dynamics and Quiescence by Netrin-1 Cytoskeletal Signaling
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Regulation of Muscle Stem Cell Dynamics and Quiescence by Netrin-1 Cytoskeletal Signaling

Hsiao-Fan Lo, Yue Lu, David Sachs, Jean-Francois Cloutier, Elizabeth Chen and Robert S. Krauss
bioRxiv
Cold Spring Harbor Laboratory, 1.1
11/03/2025
DOI: 10.1101/2025.11.01.686042
PMCID: PMC12637693
PMID: 41278717
url
https://doi.org/10.1101/2025.11.01.686042View
Preprint (Author's original) This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

The hallmark property of muscle stem cells (MuSCs) at homeostasis is quiescence. However, MuSCs have cellular protrusions that are heterogeneous, complex, and tipped with filopodia, all signs of motile structures. Such protrusions may serve as sensors of the MuSC niche. We report here development of an ex vivo live imaging assay for MuSC protrusion dynamics and its use in identification of regulatory factors in this process. The axon guidance cue Netrin-1 promotes MuSC protrusion outgrowth ex vivo in a manner dependent on its receptors Dcc and Neogenin, the small GTPase Rac1, and the actin-branching factor Arp2/3, each of which is also required for Netrin-dependent axonal growth cone motility. Adult MuSC-specific genetic removal of Netrin-1 receptors, Rac1, and Arp2/3 each result in failure to maintain homeostatic protrusion lengths and MuSC attrition. These findings reveal an unanticipated level of morphological dynamism by a quiescent stem cell at homeostasis and link this phenomenon to preservation of the quiescent state.
 Cell Biology

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