PUBLICATION

In vivo nerve-macrophage interactions following peripheral nerve injury

Authors
Rosenberg, A.F., Wolman, M.A., Franzini-Armstrong, C., and Granato, M.
ID
ZDB-PUB-120326-5
Date
2012
Source
The Journal of neuroscience : the official journal of the Society for Neuroscience   32(11): 3989-3909 (Journal)
Registered Authors
Granato, Michael, Rosenberg, Allison, Wolman, Marc
Keywords
none
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Cell Communication*/physiology
  • Cell Movement/physiology
  • Macrophages/metabolism*
  • Macrophages/pathology
  • Motor Neurons/metabolism*
  • Motor Neurons/pathology
  • Nerve Regeneration/physiology*
  • Peripheral Nerve Injuries/metabolism*
  • Peripheral Nerve Injuries/pathology
  • Wallerian Degeneration/metabolism*
  • Wallerian Degeneration/pathology
  • Zebrafish
PubMed
22423110 Full text @ J. Neurosci.
Abstract

In vertebrates, the peripheral nervous system has retained its regenerative capacity, enabling severed axons to reconnect with their original synaptic targets. While it is well documented that a favorable environment is critical for nerve regeneration, the complex cellular interactions between injured nerves with cells in their environment, as well as the functional significance of these interactions, have not been determined in vivo and in real time. Here we provide the first minute-by-minute account of cellular interactions between laser transected motor nerves and macrophages in live intact zebrafish. We show that macrophages arrive at the lesion site long before axon fragmentation, much earlier than previously thought. Moreover, we find that axon fragmentation triggers macrophage invasion into the nerve to engulf axonal debris, and that delaying nerve fragmentation in a Wlds model does not alter macrophage recruitment but induces a previously unknown ‘nerve scanning’ behavior, suggesting that macrophage recruitment and subsequent nerve invasion are controlled by separate mechanisms. Finally, we demonstrate that macrophage recruitment, thought to be dependent on Schwann cell-derived signals, occurs independently of Schwann cells. Thus, live cell imaging defines novel cellular and functional interactions between injured nerves and immune cells.

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