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In vivo cell sorting in complementary segmental domains mediated by Eph receptors and ephrins

Nature volume 399, pages 267–271 (1999)Cite this article

Abstract

The restriction of intermingling between specific cell populations is crucial for the maintenance of organized patterns during development. A striking example is the restriction of cell mixing between segments in the insect epidermis1 and the vertebrate hindbrain2 that may enable each segment to maintain a distinctidentity. In the hindbrain, this is a result of different adhesive properties of odd- and even-numbered segments (rhombomeres)3,4, but an adhesion molecule with alternating segmental expression has not been found. However, blocking experiments suggest that Eph-receptor tyrosine kinases may be required for the segmental restriction of cells5. Eph receptors and their membrane-bound ligands, ephrins, are expressed in complementary rhombomeres6 and, by analogy with their roles in axon pathfinding7,8, could mediate cell repulsion at boundaries. Remarkably, transmembrane ephrins can themselves transduce signals9,10, raising the possibility that bi-directional signalling occurs between adjacent ephrin- and Eph-receptor-expressing cells. We report here that mosaic activation of Eph receptors leads to sorting of cells to boundaries in odd-numbered rhombomeres, whereas mosaic activation of ephrins results in sorting to boundaries in even-numbered rhombomeres. These data implicate Eph receptors and ephrins in the segmental restriction of cell intermingling.

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Figure 1: Cell sorting after mosaic expression of ephrin-B2, a, Left side; diagram illustrating activation of EphA4 and EphB receptors (R) by ephrin-B2 ligand (L).
Figure 2: Activation of EphA4 and ephrin-B2 by truncated ligands.
Figure 3: Cell sorting after mosaic expression of truncated EphA4.
Figure 4: Sorting of cells adjacent to rhombomere boundaries.
Figure 5: Time-lapse analysis of cell sorting.

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Acknowledgements

We thank N. Gale and G. Yancopoulos for ephrin clones, M. Henkemeyer for the EphB2 clone and S. Fraser, J. P. Vincent, R. Krumlauf and P. Trainor for discussions. This work was supported by the MRC, an EC Biotechnology grant and an EMBO Fellowship to G.M.

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  1. Division of Developmental Neurobiology, National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA, UK

    Qiling Xu, Georg Mellitzer, Vicky Robinson & David G. Wilkinson

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  1. Qiling Xu
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  2. Georg Mellitzer
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  4. David G. Wilkinson
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Correspondence to David G. Wilkinson.

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Xu, Q., Mellitzer, G., Robinson, V. et al. In vivo cell sorting in complementary segmental domains mediated by Eph receptors and ephrins. Nature 399, 267–271 (1999). https://doi.org/10.1038/20452

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