Moore et al, 2013 (Par3 neural crest).pdf (6.52 MB)
Par3 controls neural crest migration by promoting microtubule catastrophe during contact inhibition of locomotion
journal contribution
posted on 2023-06-09, 02:17 authored by Rachel Moore, Eric Theveneau, Sara Pozzi, Paula Alexandre, Joanna Richardson, Anne Merks, Maddy Parsons, Jubin Kashef, Claudia Linker, Roberto MayorThere is growing evidence that contact inhibition of locomotion (CIL) is essential for morphogenesis and its failure is thought to be responsible for cancer invasion; however, the molecular bases of this phenomenon are poorly understood. Here we investigate the role of the polarity protein Par3 in CIL during migration of the neural crest, a highly migratory mesenchymal cell type. In epithelial cells, Par3 is localised to the cell-cell adhesion complex and is important in the definition of apicobasal polarity, but the localisation and function of Par3 in mesenchymal cells are not well characterised. We show in Xenopus and zebrafish that Par3 is localised to the cell-cell contact in neural crest cells and is essential for CIL. We demonstrate that the dynamics of microtubules are different in different parts of the cell, with an increase in microtubule catastrophe at the collision site during CIL. Par3 loss-of-function affects neural crest migration by reducing microtubule catastrophe at the site of cell-cell contact and abrogating CIL. Furthermore, Par3 promotes microtubule catastrophe by inhibiting the Rac-GEF Trio, as double inhibition of Par3 and Trio restores microtubule catastrophe at the cell contact and rescues CIL and neural crest migration. Our results demonstrate a novel role of Par3 during neural crest migration, which is likely to be conserved in other processes that involve CIL such as cancer invasion or cell dispersion.
History
Publication status
- Published
File Version
- Published version
Journal
DevelopmentISSN
0950-1991Publisher
Company of BiologistsExternal DOI
Volume
140Page range
4763-4775Department affiliated with
- Biochemistry Publications
Full text available
- Yes
Peer reviewed?
- Yes