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Scientific article
Open access
English

Motor neurons use push-pull signals to direct vascular remodeling critical for their connectivity

Published inNeuron, vol. 110, no. 24, p. 4090-4107.e11
Publication date2022-12-21
First online date2022-10-13
Abstract

The nervous system requires metabolites and oxygen supplied by the neurovascular network, but this necessitates close apposition of neurons and endothelial cells. We find motor neurons attract vessels with long-range VEGF signaling, but endothelial cells in the axonal pathway are an obstacle for establishing connections with muscles. It is unclear how this paradoxical interference from heterotypic neurovascular contacts is averted. Through a mouse mutagenesis screen, we show that Plexin-D1 receptor is required in endothelial cells for development of neuromuscular connectivity. Motor neurons release Sema3C to elicit short-range repulsion via Plexin-D1, thus displacing endothelial cells that obstruct axon growth. When this signaling pathway is disrupted, epaxial motor neurons are blocked from reaching their muscle targets and concomitantly vascular patterning in the spinal cord is altered. Thus, an integrative system of opposing push-pull cues ensures detrimental axon-endothelial encounters are avoided while enabling vascularization within the nervous system and along peripheral nerves.

eng
Keywords
  • VEGF
  • Axon guidance
  • Cell signaling
  • Cell-cell interactions
  • Forward genetics
  • Motor neurons
  • Neural circuits
  • Neurovascular patterning
  • Semaphorin/plexin
  • Spinal cord
  • Animals
  • Mice
  • Vascular Remodeling
  • Endothelial Cells / metabolism
  • Motor Neurons / metabolism
  • Axons / metabolism
  • Spinal Cord / metabolism
  • Semaphorins / metabolism
Affiliation Not a UNIGE publication
Citation (ISO format)
MARTINS, Luis et al. Motor neurons use push-pull signals to direct vascular remodeling critical for their connectivity. In: Neuron, 2022, vol. 110, n° 24, p. 4090–4107.e11. doi: 10.1016/j.neuron.2022.09.021
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Article (Accepted version)
accessLevelPublic
Identifiers
ISSN of the journal0896-6273
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