Injured axons instruct schwann cells to build constricting actin spheres to accelerate axonal disintegration

Vaquié, Adrien; Sauvain, Alizée; Duman, Mert; Nocera, Gianluigi; Egger, Boris; Meyenhofer, Felix; Falquet, Laurent; Bartesaghi, Luca; Chrast, Roman; Lamy, Christophe M.; Bang, Seokyoung; Lee, Seung-Ryeol; Jeon, Noo Li; Ruff, Sophie; Jacob, Claire

doi:10.1016/j.celrep.2019.05.060

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Injured axons instruct schwann cells to build constricting actin spheres to accelerate axonal disintegration

Vaquié, Adrien Department of Biology, University of Fribourg, Fribourg, Switzerland
Sauvain, Alizée Department of Biology, University of Fribourg, Fribourg, Switzerland
Duman, Mert Department of Biology, University of Fribourg, Fribourg, Switzerland - Department of Biology, Johannes Gutenberg University Mainz, Mainz, Germany
Nocera, Gianluigi Department of Biology, University of Fribourg, Fribourg, Switzerland - Department of Biology, Johannes Gutenberg University Mainz, Mainz, Germany
Egger, Boris Department of Biology, University of Fribourg, Fribourg, Switzerland - Bioimage Light Microscopy Facility, University of Fribourg, Fribourg, Switzerland
Meyenhofer, Felix Department of Biology, University of Fribourg, Fribourg, Switzerland - Department of Medicine, University of Fribourg, Fribourg, Switzerland - Bioimage Light Microscopy Facility, University of Fribourg, Fribourg, Switzerland
Falquet, Laurent Department of Biology, University of Fribourg, Fribourg, Switzerland - Department of Medicine, University of Fribourg, Fribourg, Switzerland - Bioinformatics Core Facility, University of Fribourg and Swiss Institute of Bioinformatics, Fribourg, Switzerland
Bartesaghi, Luca Departments of Neuroscience and Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
Chrast, Roman Departments of Neuroscience and Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
Lamy, Christophe M. Department of Medicine, University of Fribourg, Fribourg, Switzerland
Bang, Seokyoung School of Mechanical and Aerospace Engineering, Seoul National University, Seoul, South Korea
Lee, Seung-Ryeol School of Mechanical and Aerospace Engineering, Seoul National University, Seoul, South Korea
Jeon, Noo Li School of Mechanical and Aerospace Engineering, Seoul National University, Seoul, South Korea
Ruff, Sophie Department of Biology, University of Fribourg, Fribourg, Switzerland
Jacob, Claire Department of Biology, University of Fribourg, Fribourg, Switzerland - Department of Biology, Johannes Gutenberg University Mainz, Mainz, Germany

11.06.2019

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Cell Reports. - 2019, vol. 27, no. 11, p. 3152-3166.e7

English After a peripheral nerve lesion, distal ends of injured axons disintegrate into small fragments that are subsequently cleared by Schwann cells and later by macrophages. Axonal debris clearing is an early step of the repair process that facilitates regeneration. We show here that Schwann cells promote distal cut axon disintegration for timely clearing. By combining cell-based and in vivo models of nerve lesion with mouse genetics, we show that this mechanism is induced by distal cut axons, which signal to Schwann cells through PlGF mediating the activation and upregulation of VEGFR1 in Schwann cells. In turn, VEGFR1 activates Pak1, leading to the formation of constricting actomyosin spheres along unfragmented distal cut axons to mediate their disintegration. Interestingly, oligodendrocytes can acquire a similar behavior as Schwann cells by enforced expression of VEGFR1. These results thus identify controllable molecular cues of a neuron-glia crosstalk essential for timely clearing of damaged axons.

Faculty

Faculté des sciences et de médecine

Department

Département de Biologie, Département de Médecine

Language