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Development January 1, 2018; 145 (13):
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PDGF-A suppresses contact inhibition during directional collective cell migration.

Nagel M , Winklbauer R .

The leading-edge mesendoderm (LEM) of the Xenopus gastrula moves as an aggregate by collective migration. However, LEM cells on fibronectin in vitro show contact inhibition of locomotion by quickly retracting lamellipodia upon mutual contact. We found that a fibronectin-integrin-syndecan module acts between p21-activated kinase 1 upstream and ephrin B1 downstream to promote the contact-induced collapse of lamellipodia. To function in this module, fibronectin has to be present as puncta on the surface of LEM cells. To overcome contact inhibition in LEM cell aggregates, PDGF-A deposited in the endogenous substratum of LEM migration blocks the fibronectin-integrin-syndecan module at the integrin level. This stabilizes lamellipodia preferentially in the direction of normal LEM movement and supports cell orientation and the directional migration of the coherent LEM cell mass.

PubMed ID: 29884673
Article link: Development
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: bcr cdkn1a cox7a2l efnb1 fn1 itgb1 mapre1 pak1 pdgfa pdgfra sdc4
GO keywords: gastrulation with mouth forming second [+]
Antibodies: Efnb1 Ab2 Itgb1 Ab1 Pdgfra Ab1 Sdc4 Ab1
Morpholinos: cdh3 MO1 efnb1 MO1 efnb2 MO1 fn1 MO1 fn1 MO2 itgb1 MO2 sdc4 MO1 sdc4 MO2

Article Images: [+] show captions