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Development January 1, 2017; 144 (13): 2456-2468.

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 .

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.

PubMed ID: 28526750
PMC ID: PMC5536867
Article link: Development
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: akt1 akt2 cdh1 cdh2 cxcl12 itk krt12.4 odc1 pdgfa pdgfra pik3cg snai2 sox2 sox9 tbxt twist1
GO keywords: neural crest cell migration [+]
Antibodies: Akt Ab9 Akt1 Ab6 Cdh1 Ab1 Cdh2 Ab3 pdgfra Ab2
Morpholinos: pdgfa MO1 pdgfra MO1

Article Images: [+] show captions
References [+] :
Ataliotis, PDGF signalling is required for gastrulation of Xenopus laevis. 1995, Pubmed, Xenbase