Axon Growth of CNS Neurons in Three Dimensions Is Amoeboid and Independent of Adhesions.


Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
21 07 2020
Historique:
received: 27 03 2020
revised: 26 05 2020
accepted: 23 06 2020
entrez: 23 7 2020
pubmed: 23 7 2020
medline: 29 4 2021
Statut: ppublish

Résumé

During development of the central nervous system (CNS), neurons polarize and rapidly extend their axons to assemble neuronal circuits. The growth cone leads the axon to its target and drives axon growth. Here, we explored the mechanisms underlying axon growth in three dimensions. Live in situ imaging and super-resolution microscopy combined with pharmacological and molecular manipulations as well as biophysical force measurements revealed that growth cones extend CNS axons independent of pulling forces on their substrates and without the need for adhesions in three-dimensional (3D) environments. In 3D, microtubules grow unrestrained from the actomyosin cytoskeleton into the growth cone leading edge to enable rapid axon extension. Axons extend and polarize even in adhesion-inert matrices. Thus, CNS neurons use amoeboid mechanisms to drive axon growth. Together with our understanding that adult CNS axons regenerate by reactivating developmental processes, our findings illuminate how cytoskeletal manipulations enable axon regeneration in the adult CNS.

Identifiants

pubmed: 32698008
pii: S2211-1247(20)30888-3
doi: 10.1016/j.celrep.2020.107907
pii:
doi:

Substances chimiques

Actins 0
Collagen 9007-34-5
Actomyosin 9013-26-7

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

107907

Informations de copyright

Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Interests H. Witte, A. Ertürk, F. Hellal, and F.B. filed a patent on the use of microtubule-stabilizing compounds for the treatment of lesions of CNS axons (European patent number 1858498; European patent application EP 11 00 9155.0; U.S. patent application 11/908,118).

Auteurs

Telma E Santos (TE)

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

Barbara Schaffran (B)

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

Nicolas Broguière (N)

Department of Health Sciences and Technology, ETH Zürich, Otto-Stern-Weg 7, 8093 Zürich, Switzerland.

Liane Meyn (L)

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

Marcy Zenobi-Wong (M)

Department of Health Sciences and Technology, ETH Zürich, Otto-Stern-Weg 7, 8093 Zürich, Switzerland.

Frank Bradke (F)

Laboratory of Axon Growth and Regeneration, German Center for Neurodegenerative Diseases (DZNE), Venusberg-Campus 1, Building 99, 53127 Bonn, Germany. Electronic address: frank.bradke@dzne.de.

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Classifications MeSH