express ephrins. In this way we can precisely control the levels of ephrins
involved in the interaction, and investigate possible differences in response to
It is interesting to view the interaction of Eph receptor-expressing neurons
with ephrin-expressing fibroblasts in the light of the work of Michael
Abercrombie. During the phenomenon of contact inhibition of locomotion in
cultured cells, he described how dynamic actin structures such as lamellipodia
are paralysed at new cell contact sites. Overall this can lead to the migration of
contacting cells away from one another. The signalling pathways involved
must therefore converge on the actin cytoskeleton and cell adhesion systems in
both cells involved in the interaction. In the co-culture assay described here
both cells respond by remodelling their actin based motility machineries, and
ultimately pull away from the site of contact. It may turn out to be that similar
mechanisms are involved in Eph receptor/ephrin regulated cell repulsion and
Abercrombie's contact inhibition of locomotion.
Adams, R. H., Wilkinson, G. A., Weiss, C., Diella, F., et al., 1999. Roles of ephrinB ligands
and EphB receptors in cardiovascular development: demarcation of arterial/venous
domains, vascular morphogenesis, and sprouting angiogenesis. Genes Dev 13: 295-306.
Bruckner, K., Pasquale, E. B. and Klein, R., 1997. Tyrosine phosphorylation of
transmembrane ligands for Eph receptors. Science 275: 1640-1643.
Carter, N., Nakamoto, T., Hirai, H. and Hunter, T., 2002. EphrinA1-induced cytoskeletal
re-organization requires FAK and p130(cas). Nat. Cell Biol. 4: 565-573.
Cheng, H. J., Nakamoto, M., Bergemann, A. D. and Flanagan, J. G., 1995. Comple-
mentary gradients in expression and binding of ELF-1 and Mek4 in development of the
topographic retinotectal projection map. Cell 82: 371-381.
Cowan, C. A. and Henkemeyer, M., 2001. The SH2/SH3 adaptor Grb4 transduces B-
ephrin reverse signals. Nature 413: 174-179.
Dickson, B. J., 2001. Rho GTPases in growth cone guidance. Curr. Opin. Neurobiol. 11:
Drescher, U., Kremoser, C., Handwerker, C., Loschinger, J., et al., 1995. In vitro guidance
of retinal ganglion cell axons by RAGS, a 25 kDa tectal protein related to ligands for
Eph receptor tyrosine kinases. Cell 82: 359-370.
Drescher, U., Bonhoeffer, F. and Muller, B. K., 1997. The Eph family in retinal axon
guidance. Curr. Opin. Neurobiol. 7: 75-80.
Durbin, L., Brennan, C., Shiomi, K., Cooke, J., et al., 1998. Eph signaling is required for
segmentation and differentiation of the somites. Genes Dev. 12: 3096-3109.
Feldheim, D. A., Kim, Y. I., Bergemann, A. D., Frisen, J., et al., 2000. Genetic analysis of
ephrin-A2 and ephrin-A5 shows their requirement in multiple aspects of retinocollicular
mapping. Neuron 25: 563-574.
Flanagan, J. G. and Vanderhaeghen, P., 1998. The ephrins and Eph receptors in neural
development. Annu. Rev. Neurosci. 21: 309-345.