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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

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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 Mayor
There 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

Development

ISSN

0950-1991

Publisher

Company of Biologists

Volume

140

Page range

4763-4775

Department affiliated with

  • Biochemistry Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2016-07-27

First Open Access (FOA) Date

2016-07-27

First Compliant Deposit (FCD) Date

2016-07-27

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