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PDGF controls contact inhibition of locomotion by regulating N-cadherin during neural crest migration

Bahm, I; Barriga, EH; Frolov, A; Theveneau, E; Frankel, P; Mayor, R; (2017) PDGF controls contact inhibition of locomotion by regulating N-cadherin during neural crest migration. Development , 144 (13) pp. 2456-2468. 10.1242/dev.147926. Green open access

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Abstract

A fundamental property of neural crest (NC) migration is contact inhibition of locomotion (CIL), a process by which cells change their direction of migration upon cell contact. CIL has been proven to be essential for NC migration in amphibians and zebrafish by controlling cell polarity in a cell contact-dependent manner. Cell contact during CIL requires the participation of the cell adhesion molecule N-cadherin, which starts to be expressed by NC cells as a consequence of the switch between E- and N-cadherins during epithelial-to-mesenchymal transition (EMT). However, the mechanism that controls the upregulation of N-cadherin remains unknown. Here, we show that platelet-derived growth factor receptor alpha (PDGFRα) and its ligand platelet-derived growth factor A (PDGF-A) are co-expressed in migrating cranial NC. Inhibition of PDGF-A/PDGFRα blocks NC migration by inhibiting N-cadherin and, consequently, impairing CIL. Moreover, we identify phosphatidylinositol-3-kinase (PI3K)/AKT as a downstream effector of the PDGFRα cellular response during CIL. Our results lead us to propose PDGF-A/ PDGFRα signalling as a tissue-autonomous regulator of CIL by controlling N-cadherin upregulation during EMT. Finally, we show that once NC cells have undergone EMT, the same PDGF-A/PDGFRα works as an NC chemoattractant, guiding their directional migration.

Type: Article
Title: PDGF controls contact inhibition of locomotion by regulating N-cadherin during neural crest migration
Open access status: An open access version is available from UCL Discovery
DOI: 10.1242/dev.147926
Publisher version: http://dx.doi.org/10.1242/dev.147926
Language: English
Additional information: © 2017. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
Keywords: Developmental Biology, PDGF, PDGFR, Neural Crest, EMT, Contact inhibition of locomotion, N-cadherin, Migration, Xenopus, COLLECTIVE CELL-MIGRATION, EPITHELIAL-MESENCHYMAL TRANSITIONS, ZEBRAFISH EMBRYONIC-DEVELOPMENT, GROWTH-FACTOR, CRANIOFACIAL DEVELOPMENT, SIGNALING PATHWAYS, IN-VIVO, XENOPUS-LAEVIS, ALPHA-RECEPTOR, MESSENGER-RNA
UCL classification: UCL > Provost and Vice Provost Offices
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 > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Metabolism and Experi Therapeutics
URI: http://discovery.ucl.ac.uk/id/eprint/1558498
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