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.
Original language | English |
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Article number | 230037 |
Journal | Open Biology |
Volume | 13 |
Publication status | Accepted/In press - 20 Sept 2023 |
Keywords
- satellite cell
- myogenesis
- zebrafish
- cell motility
- mechanotransduction
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Dive into the research topics of 'Migration and differentiation of muscle stem cells are coupled by RhoA signalling during regeneration'. Together they form a unique fingerprint.Student theses
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Dissection of the key molecular pathways for muscle regeneration in the zebrafish in vivo model
Author: Sultan, S., 1 Jun 2022Supervisor: Knight, R. (Supervisor) & Hogstrand, C. (Supervisor)
Student thesis: Doctoral Thesis › Doctor of Philosophy
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