TY - JOUR
AU - Vieira, José Ricardo
AU - Shah, Bhavin
AU - Dupraz, Sebastian
AU - Paredes, Isidora
AU - Himmels, Patricia
AU - Schermann, Géza
AU - Adler, Heike
AU - Motta, Alessia
AU - Gärtner, Lea
AU - Navarro-Aragall, Ariadna
AU - Ioannou, Elena
AU - Dyukova, Elena
AU - Bonnavion, Remy
AU - Fischer, Andreas
AU - Bonanomi, Dario
AU - Bradke, Frank
AU - Ruhrberg, Christiana
AU - Ruiz de Almodóvar, Carmen
TI - Endothelial PlexinD1 signaling instructs spinal cord vascularization and motor neuron development.
JO - Neuron
VL - 110
IS - 24
SN - 0896-6273
CY - New York, NY
PB - Elsevier
M1 - DKFZ-2022-03173
SP - 4074 - 4089.e6
PY - 2022
AB - 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.
KW - Animals
KW - Mice
KW - Endothelial Cells
KW - Motor Neurons: physiology
KW - Spinal Cord
KW - Signal Transduction
KW - Axons
KW - Mice, Knockout
KW - CNS vascularization (Other)
KW - PlexinD1 (Other)
KW - Sema3C (Other)
KW - blood vessel (Other)
KW - endothelial cell (Other)
KW - motor neuron (Other)
KW - neuro-vascular communication (Other)
KW - neurodevelopment (Other)
KW - spinal cord (Other)
LB - PUB:(DE-HGF)16
C6 - pmid:36549270
DO - DOI:10.1016/j.neuron.2022.12.005
UR - https://inrepo02.dkfz.de/record/186452
ER -