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PLoS Biol September 1, 2014; 12 (9): e1001955.

Variable combinations of specific ephrin ligand/Eph receptor pairs control embryonic tissue separation.

Rohani N , Parmeggiani A , Winklbauer R , Fagotto F .

Ephrins and Eph receptors are involved in the establishment of vertebrate tissue boundaries. The complexity of the system is puzzling, however in many instances, tissues express multiple ephrins and Ephs on both sides of the boundary, a situation that should in principle cause repulsion between cells within each tissue. Although co-expression of ephrins and Eph receptors is widespread in embryonic tissues, neurons, and cancer cells, it is still unresolved how the respective signals are integrated into a coherent output. We present a simple explanation for the confinement of repulsion to the tissue interface: Using the dorsal ectoderm-mesoderm boundary of the Xenopus embryo as a model, we identify selective functional interactions between ephrin-Eph pairs that are expressed in partial complementary patterns. The combined repulsive signals add up to be strongest across the boundary, where they reach sufficient intensity to trigger cell detachments. The process can be largely explained using a simple model based exclusively on relative ephrin and Eph concentrations and binding affinities. We generalize these findings for the ventral ectoderm-mesoderm boundary and the notochord boundary, both of which appear to function on the same principles. These results provide a paradigm for how developmental systems may integrate multiple cues to generate discrete local outcomes.

PubMed ID: 25247423
PMC ID: PMC4172438
Article link: PLoS Biol
Grant support: [+]
Genes referenced: cdh3 ctrl efnb1 efnb2 efnb3 epha4 ephb2 ephb4 fn1 foxa4 fuz mapre2 mlc1 myc ptpn11
Morpholinos: efnb1 MO1 efnb2 MO1 efnb3 MO1 epha4 MO1 ephb2 MO1 ephb4 MO1

Article Images: [+] show captions
References [+] :
Armes, The ALK-2 and ALK-4 activin receptors transduce distinct mesoderm-inducing signals during early Xenopus development but do not co-operate to establish thresholds. 1997, Pubmed, Xenbase

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