Yoshida Lab
News & Impact

You are here

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

Journal Article
Luis F Martins, Ilaria Brambilla, Alessia Motta, Stefano de Pretis, Ganesh Parameshwar Bhat, Aurora Badaloni, Chiara Malpighi, Neal D Amin, Fumiyasu Imai, Ramiro D Almeida, Yutaka Yoshida, Samuel L Pfaff, Dario Bonanomi
Year Published: 
Neuron. 2022 Oct 7;S0896-6273(22)00860-1. doi: 10.1016/j.neuron.2022.09.021. Online ahead of print.
PMID: 36240771 | DOI: 10.1016/j.neuron.2022.09.021
Full-Text on Cell


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.


Conditions & Recovery

Spinal Cord Injury icon
Around the world, between 300,000 and 500,000 people are living with a SCI.
Motor Recovery Icon
Write and walk again.