PUBLICATION

Migration and differentiation of muscle stem cells are coupled by RhoA signalling during regeneration

Authors
Brondolin, M., Herzog, D., Sultan, S., Warburton, F., Vigilante, A., Knight, R.D.
ID
ZDB-PUB-231002-59
Date
2023
Source
Open Biology   13: 230037230037 (Journal)
Registered Authors
Knight, Robert
Keywords
cell motility, mechanotransduction, myogenesis, satellite cell, zebrafish
MeSH Terms
  • Adult Stem Cells*
  • Animals
  • Cell Differentiation
  • Muscle, Skeletal
  • Signal Transduction
  • Zebrafish*
PubMed
37726092 Full text @ Open Biol.
Abstract
Skeletal muscle is highly regenerative and is mediated by a population of migratory adult muscle stem cells (muSCs). Effective muscle regeneration requires a spatio-temporally regulated response of the muSC population to generate sufficient muscle progenitor cells that then differentiate at the appropriate time. The relationship between muSC migration and cell fate is poorly understood and it is not clear how forces experienced by migrating cells affect cell behaviour. We have used zebrafish to understand the relationship between muSC cell adhesion, behaviour and fate in vivo. Imaging of pax7-expressing muSCs as they respond to focal injuries in trunk muscle reveals that they migrate by protrusive-based means. By carefully characterizing their behaviour in response to injury we find that they employ an adhesion-dependent mode of migration that is regulated by the RhoA kinase ROCK. Impaired ROCK activity results in reduced expression of cell cycle genes and increased differentiation in regenerating muscle. This correlates with changes to focal adhesion dynamics and migration, revealing that ROCK inhibition alters the interaction of muSCs to their local environment. We propose that muSC migration and differentiation are coupled processes that respond to changes in force from the environment mediated by RhoA signalling.
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