Eph Receptors and Ephrins Are Key Regulators of Morphogenesis 141
tern but it is also important to be aware that Eph/ephrin signalling is
centrally involved in other developmental processes. These include gastrulation, where there is growing evidence for a role for Eph/ephrin
signalling in the primary movement of cells during convergence and
extension of the vertebrate embryo (Winning et al. 1996; Jones et al.
1998). It is also clear that Eph/ephrin signalling is involved in the
formation of blood vessels within the embryo (Wang et al. 1998), as
ephrin-B2 loss-of-function mutants, produced by targeted disruption of
the mouse ephrin-B2 gene, have an abnormal embryonic vasculature.
Examination of Eph/ephrin function with regard to these diverse processes indicates that signalling through these receptor tyrosine kinases
and the class B ephrins controls cellular morphology. In the case of the
growth cone and the neural crest cell, guidance is achieved by repulsive
interactions between receptor-expressing and ligand-expressing cells
which occupy reciprocal spatial domains in the tissues of the embryo.
Questions remain concerning the intracellular pathways linking Eph
receptor/ephrin signalling to the cytoskeleton. Our understanding of the
specificity of cellular responses to this large group of receptors will be
resolved as the intracellular pathways are defined and the structural
features of the receptor and ligand proteins are understood. Little is
known about the upstream regulation of the Eph receptor and ephrin
genes. The dynamic nature of their expression and the changes in
expression of different members of the class A and class B families
between species pose interesting questions in this regard.
References
Bartley TD, Hunt RW, Welcher AA, Boyle WJ, Parker VP, Lindberg RA, Lu
HS, Colombero AM, Elliot RA, Guthrie BA, Holst PL, Skrine JD, Toso RJ,
Zhang M, Fernandez E, Trail G, Hunter T, Fox GM (1994) B61 is a ligand
for the ECK receptor protein-tyrosine kinase. Nature 368:558-560
Bergemann A, Hwai-Jong C, Brambilla R, Klein R, Flanagan J (1995) Elf-2, a
new member of the Eph ligand family, is segmentally expressed in mouse
embryos in the region of the hindbrain and newly forming somites. Mol
Cell Bioi 15:4921-4929
Brambilla R, Schnapp A, Casagranda F, Labrador J, Bergeman A, Flanagan J,
Pasquale E, Klein R (1995) Membrane bound LERK2 ligand can signal
tern but it is also important to be aware that Eph/ephrin signalling is
centrally involved in other developmental processes. These include gastrulation, where there is growing evidence for a role for Eph/ephrin
signalling in the primary movement of cells during convergence and
extension of the vertebrate embryo (Winning et al. 1996; Jones et al.
1998). It is also clear that Eph/ephrin signalling is involved in the
formation of blood vessels within the embryo (Wang et al. 1998), as
ephrin-B2 loss-of-function mutants, produced by targeted disruption of
the mouse ephrin-B2 gene, have an abnormal embryonic vasculature.
Examination of Eph/ephrin function with regard to these diverse processes indicates that signalling through these receptor tyrosine kinases
and the class B ephrins controls cellular morphology. In the case of the
growth cone and the neural crest cell, guidance is achieved by repulsive
interactions between receptor-expressing and ligand-expressing cells
which occupy reciprocal spatial domains in the tissues of the embryo.
Questions remain concerning the intracellular pathways linking Eph
receptor/ephrin signalling to the cytoskeleton. Our understanding of the
specificity of cellular responses to this large group of receptors will be
resolved as the intracellular pathways are defined and the structural
features of the receptor and ligand proteins are understood. Little is
known about the upstream regulation of the Eph receptor and ephrin
genes. The dynamic nature of their expression and the changes in
expression of different members of the class A and class B families
between species pose interesting questions in this regard.
References
Bartley TD, Hunt RW, Welcher AA, Boyle WJ, Parker VP, Lindberg RA, Lu
HS, Colombero AM, Elliot RA, Guthrie BA, Holst PL, Skrine JD, Toso RJ,
Zhang M, Fernandez E, Trail G, Hunter T, Fox GM (1994) B61 is a ligand
for the ECK receptor protein-tyrosine kinase. Nature 368:558-560
Bergemann A, Hwai-Jong C, Brambilla R, Klein R, Flanagan J (1995) Elf-2, a
new member of the Eph ligand family, is segmentally expressed in mouse
embryos in the region of the hindbrain and newly forming somites. Mol
Cell Bioi 15:4921-4929
Brambilla R, Schnapp A, Casagranda F, Labrador J, Bergeman A, Flanagan J,
Pasquale E, Klein R (1995) Membrane bound LERK2 ligand can signal