RT Journal Article
SR Electronic
T1 N-cadherin-Presented Slit Repulsive-Cues Direct Collective Schwann cell Migration
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 549030
DO 10.1101/549030
A1 Julian J.A Hoving
A1 Elizabeth Harford-Wright
A1 Patrick Wingfield-Digby
A1 Anne-Laure Cattin
A1 Mariana Campana
A1 Toby Morgan
A1 Victor Quereda
A1 Erica Torchiaro
A1 Alison C. Lloyd
YR 2019
UL http://biorxiv.org/content/early/2019/02/13/549030.abstract
AB Collective cell migration is fundamental for the development of organisms and in the adult, for tissue regeneration and in pathological conditions such as cancer. Migration as a coherent group requires the maintenance of cell-cell interactions, while contact-inhibition-of-locomotion (CIL), a local repulsive force, propels the group forward. Here we show that the cell-cell interaction molecule, N-cadherin, regulates both adhesion and repulsion processes during Schwann cell collective migration, which is required for peripheral nerve regeneration. However, distinct from its role in cell-cell adhesion, the repulsion process is independent of N-cadherin trans-homodimerisation and the associated adherens junction complex. Rather, the extracellular domain of N-cadherin acts to traffic a repulsive Slit2/Slit3 signal to the cell-surface. Inhibiting Slit2/Slit3 signalling inhibits CIL and subsequently collective SC migration, resulting in adherent, non-migratory cell clusters. These findings provide insight into how opposing signals can mediate collective cell migration and how CIL pathways are promising targets for inhibiting pathological cell migration.