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  4. Injury-induced Erk1/2 signaling tissue-specifically interacts with Ca2+ activity and is necessary for regeneration of spinal cord and skeletal muscle

Injury-induced Erk1/2 signaling tissue-specifically interacts with Ca2+ activity and is necessary for regeneration of spinal cord and skeletal muscle

Cell Calcium, 2022 · DOI: 10.1016/j.ceca.2022.102540 · Published: March 1, 2022

Regenerative MedicineGenetics

Simple Explanation

Stem cells' transition from quiescence to proliferation enables tissues to self-repair after injury. The activation of the Erk1/2 signaling pathway in neural and muscle stem cells is necessary for cell proliferation and regeneration of spinal cord and skeletal muscle. This study found that after tail amputation in Xenopus laevis larvae, both Ca2+ and Erk1/2 signaling pathways are activated. Precise temporal and tissue-specific activation of these pathways is essential for regulating spinal cord and muscle regeneration. Erk1/2 activity is necessary for an injury-induced increase in intracellular store-dependent Ca2+ dynamics in skeletal muscle, but in spinal cord, injury increases Ca2+ influx-dependent Ca2+ activity independent of Erk1/2 signaling.

Study Duration
Not specified
Participants
Xenopus laevis larvae
Evidence Level
In vivo study

Key Findings

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    Erk1/2 signaling is activated in neural and muscle stem cells of regenerating tissues and is necessary for the regeneration of both spinal cord and muscle.
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    Injury induces an increase in Ca2+ dynamics that persists in regenerating tissues and its interaction with Erk1/2 signaling occurs in a tissue-specific manner.
  • 3
    In muscle satellite cells, Erk1/2 signaling is specifically activated in the regenerate and in the stump adjacent to the amputation.

Research Summary

This study demonstrates that Erk1/2 activation in neural and muscle stem cells in response to injury is necessary for cell proliferation and regeneration of spinal cord and skeletal muscle in Xenopus laevis larvae. The study determined the spatiotemporal pattern of Ca2+ activity in vivo during regeneration and its interaction with Erk1/2 signaling in a tissue-specific manner. Spinal cord-specific reduction in Erk1/2 signaling mimicked the effects of global inhibition on spinal cord and notochord regeneration, but not muscle regeneration, suggesting that Erk1/2 activation may be independently necessary in spinal cord and muscle for proficient regeneration.

Practical Implications

Therapeutic Strategies

Understanding the signaling mechanisms engaged in stem cells is vital to devising therapeutic strategies to enhance tissue regeneration.

Drug targets

Targeting Erk1/2 and Ca2+ signaling pathways may offer therapeutic interventions for promoting tissue repair.

Regeneration potential

Manipulating Erk1/2 activation in both neural and muscle stem cells could trigger their respective regenerative potential.

Study Limitations

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