Endothelial PlexinD1 signaling instructs spinal cord vascularization and motor neuron development.

CNS vascularization PlexinD1 Sema3C blood vessel endothelial cell motor neuron neuro-vascular communication neurodevelopment spinal cord

Journal

Neuron
ISSN: 1097-4199
Titre abrégé: Neuron
Pays: United States
ID NLM: 8809320

Informations de publication

Date de publication:
21 12 2022
Historique:
received: 25 05 2022
revised: 04 11 2022
accepted: 03 12 2022
entrez: 22 12 2022
pubmed: 23 12 2022
medline: 27 12 2022
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 36549270
pii: S0896-6273(22)01078-9
doi: 10.1016/j.neuron.2022.12.005
pmc: PMC9796814
pii:
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

4074-4089.e6

Subventions

Organisme : Wellcome Trust
ID : 205099/Z/16/Z
Pays : United Kingdom
Organisme : British Heart Foundation
ID : FS/19/29/34367
Pays : United Kingdom

Informations de copyright

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

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Auteurs

José Ricardo Vieira (JR)

European Center for Angioscience, Medical Faculty Mannheim, Heidelberg University, Ludolf-Krehl-Straße 13-17, 68167 Mannheim, Germany; Faculty of Biosciences, Heidelberg University, Im Neuenheimer 234, 69120 Heidelberg, Germany.

Bhavin Shah (B)

European Center for Angioscience, Medical Faculty Mannheim, Heidelberg University, Ludolf-Krehl-Straße 13-17, 68167 Mannheim, Germany.

Sebastian Dupraz (S)

Institute for Neurovascular Cell Biology, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany.

Isidora Paredes (I)

European Center for Angioscience, Medical Faculty Mannheim, Heidelberg University, Ludolf-Krehl-Straße 13-17, 68167 Mannheim, Germany; Faculty of Biosciences, Heidelberg University, Im Neuenheimer 234, 69120 Heidelberg, Germany.

Patricia Himmels (P)

Faculty of Biosciences, Heidelberg University, Im Neuenheimer 234, 69120 Heidelberg, Germany.

Géza Schermann (G)

European Center for Angioscience, Medical Faculty Mannheim, Heidelberg University, Ludolf-Krehl-Straße 13-17, 68167 Mannheim, Germany; Institute for Neurovascular Cell Biology, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany.

Heike Adler (H)

European Center for Angioscience, Medical Faculty Mannheim, Heidelberg University, Ludolf-Krehl-Straße 13-17, 68167 Mannheim, Germany.

Alessia Motta (A)

San Raffaele Scientific Institute, Division of Neuroscience, via Olgettina 60, 20132 Milan, Italy.

Lea Gärtner (L)

European Center for Angioscience, Medical Faculty Mannheim, Heidelberg University, Ludolf-Krehl-Straße 13-17, 68167 Mannheim, Germany.

Ariadna Navarro-Aragall (A)

UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, EC1V 9EL London, UK.

Elena Ioannou (E)

UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, EC1V 9EL London, UK.

Elena Dyukova (E)

Max-Planck-Institute for Heart and Lung Research, Ludwigstr. 43, 61231 Bad Nauheim, Germany.

Remy Bonnavion (R)

Max-Planck-Institute for Heart and Lung Research, Ludwigstr. 43, 61231 Bad Nauheim, Germany.

Andreas Fischer (A)

Department of Clinical Chemistry, University Medical Center Göttingen, Robert-Koch-Straße 40, 37075 Göttingen, Germany; Division Vascular Signaling and Cancer, German Cancer Research Center Heidelberg, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.

Dario Bonanomi (D)

San Raffaele Scientific Institute, Division of Neuroscience, via Olgettina 60, 20132 Milan, Italy.

Frank Bradke (F)

Laboratory of Axon Growth and Regeneration, German Center for Neurodegenerative Diseases (DZNE), Venusberg Campus 1/99, 53127 Bonn, Germany.

Christiana Ruhrberg (C)

UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, EC1V 9EL London, UK.

Carmen Ruiz de Almodóvar (C)

European Center for Angioscience, Medical Faculty Mannheim, Heidelberg University, Ludolf-Krehl-Straße 13-17, 68167 Mannheim, Germany; Institute for Neurovascular Cell Biology, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany; Schlegel Chair for Neurovascular Cell Biology, University of Bonn, Venusberg-Campus 1, 53127 Bonn, Germany. Electronic address: carmen.ruizdealmodovar@ukbonn.de.

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