ALK4/5-dependent TGF-β signaling contributes to the crosstalk between neurons and microglia following axonal lesion

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Antonella Raffo-Romero1,2, Tanina Arab1,2, Christelle Van Camp1,2

  • 1University Lille, Inserm, U-1192 - Laboratoire Protéomique, Réponse Inflammatoire et Spectrométrie de Masse-PRISM, F-59000, Lille, France.

Scientific Reports
|May 5, 2019
PubMed

Insights

In leech brains, neurons and microglia use ALK4/5 signaling for mutual communication after injury. This pathway is crucial for sequential microglia recruitment and subsequent axon regeneration.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Immunology

Background:

  • Microglia are the primary immune cells in the central nervous system (CNS), influencing neuronal activity.
  • In the medicinal leech CNS, microglia are unique in their ability to migrate to injury sites.
  • Microglia-neuron interactions are vital for neuroprotection and axonal repair in leeches due to the absence of other glial types.

Purpose of the Study:

  • To investigate the role of ALK4/5 signaling in microglia-neuron interactions following axonal injury in the leech CNS.
  • To elucidate the sequential signaling events between neurons and microglia during the response to CNS injury.

Main Methods:

  • Utilized the medicinal leech model system.
  • Investigated the expression and function of ALK4/5 signaling pathway components.
  • Examined the recruitment dynamics of microglia to the lesion site.

Main Results:

  • Injured axons release nGDF, initiating the recruitment of ALK4/5+ microglia.
  • Microglia-derived nGDF subsequently activates ALK4/5+ neurons.
  • This reciprocal signaling maintains later microglia accumulation at the lesion site.
  • ALK4/5 signaling is essential for the timely and sequential mobilization of microglia, promoting axon regeneration.

Conclusions:

  • The ALK4/5 signaling pathway is critical for the neuroprotective response to axonal injury in the leech CNS.
  • This pathway mediates essential crosstalk between neurons and microglia, orchestrating a sequential recruitment process.
  • Findings provide new insights into the conserved role of TGF-β receptor signaling in CNS injury repair.

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