Myostatin is a negative regulator of adult neurogenesis after spinal cord injury in zebrafish

Cell Reports, 2022 · DOI: 10.1016/j.celrep.2022.111705 · Published: November 22, 2022

Spinal Cord Injury Regenerative Medicine

Simple Explanation

This study investigates the role of myostatin b (mstnb) in spinal cord regeneration in zebrafish. Researchers found that mstnb is expressed in a specific population of progenitor cells after spinal cord injury. They discovered that mstnb mutants showed impaired functional recovery after spinal cord injury. The study further revealed that mstnb mutants exhibit increased neuronal differentiation in the spinal cord after injury. Molecular analysis showed that neuron differentiation genes are upregulated in mstnb mutants, suggesting that mstnb normally acts to restrain neurogenesis. Researchers found that the neural stem cell maintenance gene fgf1b is downregulated in mstnb mutants. Treatment with human fibroblast growth factor 1 (FGF1) rescued the molecular and cellular phenotypes observed in mstnb mutants, indicating a link between mstnb and FGF1 signaling in regulating neurogenesis.

Study Duration

Not specified

Participants

Adult zebrafish

Evidence Level

Not specified

Key Findings

1
Myostatin b (mstnb) is dynamically expressed in dorsal spinal cord progenitors after injury in zebrafish.
2
mstnb mutants display impaired functional recovery following spinal cord injury, despite normal glial and axonal bridging.
3
Loss of mstnb function leads to increased neuronal differentiation and upregulation of neuron differentiation genes, with fgf1b being downregulated.

Research Summary

This study supports a model where mstnb functions as a negative regulator of neuronal differentiation in rostral SC tissue after injury and suggests that mstnb-dependent FGF signaling promotes self-renewal at the expense of adult neurogenesis. SCI alters the strength and relative locations of E/I inputs by disrupting descending hindbrain connections and promoting waves of axonal degeneration, neuronal death, and demyelination. Our findings support the emergence of a lineage-restricted, neurogenic niche of dorsal progenitors during SC regeneration in zebrafish.

Practical Implications

Understanding Neurogenesis Regulation

This research provides insights into the molecular mechanisms regulating adult neurogenesis in the context of spinal cord injury, potentially leading to new therapeutic strategies.

Potential Therapeutic Targets

Identifying mstnb and FGF signaling as key regulators opens avenues for targeted interventions to enhance spinal cord repair and functional recovery.

Comparative Regeneration Studies

The study highlights differences between zebrafish and mammalian spinal cord regeneration, suggesting targets for promoting neurogenesis in mammals.

Study Limitations

1
Mechanisms underlying E/I balance disruption in mstnb mutants require further investigation.
2
The molecular identity and cellular contributions of mstnb+ progenitors need to be investigated.
3
The exact mechanisms by which local neurogenesis affects functional regeneration remain unknown.

Your Feedback

Was this summary helpful?

Back to Spinal Cord Injury