Variable Combinations of Specific Ephrin Ligand/Eph Receptor Pairs Control Embryonic Tissue Separation

• DOI: 10.1371/journal.pbio.1001955
• Publication Date: 2014-09-23T17:46:36Z
• Authors: Nazanin Rohani; Andrea Parmeggiani; Rudolf Winklbauer; François Fagotto
• Keywords: 570; Embryo, Nonmammalian; QH301-705.5; Receptor, EphB2; Xenopus; [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph]; Receptor, EphB4; Notochord; 610; Ephrin-B3; [SDV.CAN]Life Sciences [q-bio]/Cancer; Ephrin-B2; [NLIN.NLIN-CG] Nonlinear Sciences [physics]/Cellular Automata and Lattice Gases [nlin.CG]; [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]; Ephrin-B1; Mesoderm; Mice; Xenopus laevis; [NLIN.NLIN-AO] Nonlinear Sciences [physics]/Adaptation and Self-Organizing Systems [nlin.AO]; [SDV.CAN] Life Sciences [q-bio]/Cancer; Ectoderm; [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]; Morphogenesis; Animals; [NLIN.NLIN-CG]Nonlinear Sciences [physics]/Cellular Automata and Lattice Gases [nlin.CG]; Phosphorylation; Biology (General); [NLIN.NLIN-AO]Nonlinear Sciences [physics]/Adaptation and Self-Organizing Systems [nlin.AO]; Complement receptors; [PHYS.PHYS.PHYS-BIO-PH] Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph]; [PHYS.PHYS.PHYS-SOC-PH]Physics [physics]/Physics [physics]/Physics and Society [physics.soc-ph]; Embryos; Receptor, EphA4; Gene Expression Regulation, Developmental; [SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN]; Cadherins; Recombinant Proteins; [SDV.BBM.MN] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN]; [PHYS.PHYS.PHYS-SOC-PH] Physics [physics]/Physics [physics]/Physics and Society [physics.soc-ph]; Notochords; Research Article; Signal Transduction

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.