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Macrophage-Derived Slit3 Controls Cell Migration and Axon Pathfinding in the Peripheral Nerve Bridge

Dun, X-P; Carr, L; Woodley, PK; Barry, RW; Drake, LK; Mindos, T; Roberts, SL; ... Parkinson, DB; + view all (2019) Macrophage-Derived Slit3 Controls Cell Migration and Axon Pathfinding in the Peripheral Nerve Bridge. Cell Reports , 26 (6) 1458-1472.e4. 10.1016/j.celrep.2018.12.081. Green open access

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Abstract

Slit-Robo signaling has been characterized as a repulsive signal for precise axon pathfinding and cell migration during embryonic development. Here, we describe a role for Sox2 in the regulation of Robo1 in Schwann cells and for Slit3-Robo1 signaling in controlling axon guidance within the newly formed nerve bridge following peripheral nerve transection injury. In particular, we show that macrophages form the outermost layer of the nerve bridge and secrete high levels of Slit3, while migratory Schwann cells and fibroblasts inside the nerve bridge express the Robo1 receptor. In line with this pattern of Slit3 and Robo1 expression, we observed multiple axon regeneration and cell migration defects in the nerve bridge of Sox2-, Slit3-, and Robo1-mutant mice. Our findings have revealed important functions for macrophages in the peripheral nervous system, utilizing Slit3-Robo1 signaling to control correct peripheral nerve bridge formation and precise axon targeting to the distal nerve stump following injury.

Type: Article
Title: Macrophage-Derived Slit3 Controls Cell Migration and Axon Pathfinding in the Peripheral Nerve Bridge
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.celrep.2018.12.081
Publisher version: https://doi.org/10.1016/j.celrep.2018.12.081
Language: English
Additional information: Crown Copyright © 2018. This is an open access article under the CC BY license (http://creativecommons.org/ licenses/by/4.0/).
Keywords: Robo1, Schwann cell, Slit3, Sox2, fibroblast, injury, macrophages, migration, peripheral nerve, regeneration
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10067883
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