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  4. Notch Signaling Controls Generation of Motor Neurons in the Lesioned Spinal Cord of Adult Zebrafish

Notch Signaling Controls Generation of Motor Neurons in the Lesioned Spinal Cord of Adult Zebrafish

The Journal of Neuroscience, 2012 · DOI: 10.1523/JNEUROSCI.6398-11.2012 · Published: February 29, 2012

Spinal Cord InjuryRegenerative MedicineNeurology

Simple Explanation

In mammals, increased Notch signaling is thought to contribute to the lack of neurogenesis after spinal cord injury. This study investigates this in zebrafish, which can regenerate neurons after spinal injuries. The researchers found that the Notch pathway is reactivated in zebrafish after spinal cord injury. However, when they increased Notch activity, it reduced the production of new motor neurons. Conversely, blocking the Notch pathway increased the number of new motor neurons. This suggests that Notch signaling normally inhibits motor neuron regeneration in the zebrafish spinal cord.

Study Duration
Not specified
Participants
Zebrafish
Evidence Level
Not specified

Key Findings

  • 1
    Notch pathway genes are upregulated after spinal lesion in specific dorsoventral domains around the ventricle, reflecting the dorsoventral polarity of the adult progenitor domains.
  • 2
    Overactivation of Notch signaling strongly inhibits the generation of new motor neurons in the lesioned spinal cord of adult zebrafish.
  • 3
    Pharmacological inhibition of Notch signaling with DAPT augments progenitor proliferation and motor neuron generation in the lesioned spinal cord.

Research Summary

This study investigates the role of Notch signaling in motor neuron regeneration in the lesioned spinal cord of adult zebrafish. The researchers found that increased Notch signaling attenuates proliferation of progenitor cells and motor neuron generation. Pharmacologically blocking Notch signaling increases motor neuron generation, suggesting that Notch is a negative regulator of regenerative neurogenesis.

Practical Implications

Therapeutic Potential

Inhibiting Notch signaling may promote motor neuron regeneration after spinal cord injury.

Understanding Regeneration

Precise regulation of Notch activity is necessary to allow neurogenesis while maintaining the progenitor pool in the lesioned CNS.

Drug Development

Pharmacological intervention with the Notch inhibitor DAPT may inform future therapeutic interventions in the lesioned spinal cord of mammals.

Study Limitations

  • 1
    The study was conducted on zebrafish, and results may not directly translate to mammals.
  • 2
    The precise mechanisms by which Notch signaling regulates motor neuron regeneration are not fully elucidated.
  • 3
    Increased numbers of motor neurons after DAPT treatment did not improve recovery of fish from the spinal lesion.

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