eprintid: 1558498 rev_number: 33 eprint_status: archive userid: 608 dir: disk0/01/55/84/98 datestamp: 2017-06-03 21:34:42 lastmod: 2022-01-10 00:31:55 status_changed: 2017-07-21 11:22:40 type: article metadata_visibility: show creators_name: Bahm, I creators_name: Barriga, EH creators_name: Frolov, A creators_name: Theveneau, E creators_name: Frankel, P creators_name: Mayor, R title: PDGF controls contact inhibition of locomotion by regulating N-cadherin during neural crest migration ispublished: pub divisions: UCL divisions: B02 divisions: C08 divisions: D09 divisions: F96 divisions: D14 divisions: GA2 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 note: © 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. 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. date: 2017-07-01 date_type: published publisher: COMPANY OF BIOLOGISTS LTD official_url: http://dx.doi.org/10.1242/dev.147926 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green article_type_text: Article verified: verified_manual elements_id: 1297121 doi: 10.1242/dev.147926 lyricists_name: Barriga, Elias Hernan lyricists_name: Frankel, Paul lyricists_name: Mayor, Roberto lyricists_id: EHBAR83 lyricists_id: PFRAN76 lyricists_id: RMAYO52 actors_name: Dewerpe, Marie actors_id: MDDEW97 actors_role: owner full_text_status: public publication: Development volume: 144 number: 13 pagerange: 2456-2468 pages: 13 issn: 1477-9129 citation: 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 <https://doi.org/10.1242/dev.147926>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/1558498/1/Frankel_2456.full.pdf