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Endothelial PlexinD1 signaling instructs spinal cord vascularization and motor neuron development

Vieira, JR; Shah, B; Dupraz, S; Paredes, I; Himmels, P; Schermann, G; Adler, H; ... Ruiz de Almodóvar, C; + view all (2022) Endothelial PlexinD1 signaling instructs spinal cord vascularization and motor neuron development. Neuron , 110 (24) 4074-4089.e6. 10.1016/j.neuron.2022.12.005. Green open access

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Abstract

How the vascular and neural compartment cooperate to achieve such a complex and highly specialized structure as the central nervous system is still unclear. Here, we reveal a crosstalk between motor neurons (MNs) and endothelial cells (ECs), necessary for the coordinated development of MNs. By analyzing cell-to-cell interaction profiles of the mouse developing spinal cord, we uncovered semaphorin 3C (Sema3C) and PlexinD1 as a communication axis between MNs and ECs. Using cell-specific knockout mice and in vitro assays, we demonstrate that removal of Sema3C in MNs, or its receptor PlexinD1 in ECs, results in premature and aberrant vascularization of MN columns. Those vascular defects impair MN axon exit from the spinal cord. Impaired PlexinD1 signaling in ECs also causes MN maturation defects at later stages. This study highlights the importance of a timely and spatially controlled communication between MNs and ECs for proper spinal cord development.

Type: Article
Title: Endothelial PlexinD1 signaling instructs spinal cord vascularization and motor neuron development
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.neuron.2022.12.005
Publisher version: https://doi.org/10.1016/j.neuron.2022.12.005
Language: English
Additional information: © 2022 The Authors. Published by Elsevier Inc. https://doi.org/10.1016/j.neuron.2022.12.005
Keywords: CNS vascularization, PlexinD1, Sema3C, blood vessel, endothelial cell, motor neuron, neuro-vascular communication, neurodevelopment, spinal cord, Animals, Mice, Endothelial Cells, Motor Neurons, Spinal Cord, Signal Transduction, Axons, Mice, Knockout
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/10162604
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