Macrophage-induced blood vessels guide Schwann cell-mediated regeneration of peripheral nerves

Cattin, Anne-Laure, Burden, Jemima J., Van Emmenis, Lucie, Mackenzie, Francesca E., Hoving, Julian J.A., Garcia Calavia, Noelia, Guo, Yanping, McLaughlin, Maeve, Rosenberg, Laura H., Quereda, Victor, Jamecna, Denisa, Napoli, Ilaria, Parrinello, Simona, Enver, Tariq, Ruhrberg, Christiana and Lloyd, Alison C. (2015) Macrophage-induced blood vessels guide Schwann cell-mediated regeneration of peripheral nerves. Cell, 162(5), pp. 1127-1139. ISSN (print) 0092-8674

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Abstract

The peripheral nervous system has remarkable regenerative capacities in that it can repair a fully cut nerve. This requires Schwann cells to migrate collectively to guide regrowing axons across a 'bridge' of new tissue, which forms to reconnect a severed nerve. Here we show that blood vessels direct the migrating cords of Schwann cells. This multicellular process is initiated by hypoxia, selectively sensed by macrophages within the bridge, which via VEGF-A secretion induce a polarized vasculature that relieves the hypoxia. Schwann cells then use the blood vessels as "tracks" to cross the bridge taking regrowing axons with them. Importantly, disrupting the organization of the newly formed blood vessels in vivo, either by inhibiting the angiogenic signal or by re-orienting them, compromises Schwann cell directionality resulting in defective nerve repair. This study provides important insights into how the choreography of multiple cell-types is required for the regeneration of an adult tissue.

Item Type: Article
Additional Information: This work was supported by Cancer Research UK [grant number: C378/A17135], Worldwide Cancer Research, the Biotechnology and Biological Sciences Research Council [grant number: BB/J00930X/1] and the Rosetrees Trust [grant number: A533].
Research Area: Biological sciences
Psychiatry, neuroscience and clinical psychology
Faculty, School or Research Centre: Faculty of Science, Engineering and Computing (until 2017) > School of Life Sciences
Faculty of Science, Engineering and Computing (until 2017) > School of Pharmacy and Chemistry
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Depositing User: Francesca Mackenzie
Date Deposited: 16 Nov 2017 14:01
Last Modified: 06 Sep 2019 09:40
URI: http://eprints.kingston.ac.uk/id/eprint/39939

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