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N. Holder et al.
injected with the dominant-negative EphA4 RNA, the forebrain regions
fated to become ventral diencephalon become retina instead and large
expanded eyes are formed. Again, the exact role of EphA4 in the
regionalisation process is unclear, however, since extensive morphogenetic movements underlie the development of eye and ventral diencephalic tissue, an involvement of EphA4 in cell association or
boundary formation is possible.
8.5 Principles of Eph/Ephrin Signalling
Eph receptor/ephrin signalling has been linked to a range of cellular
responses including the control of cell movement, cell shape changes
and cell growth. This raises questions as to how the specificity of
response is achieved. For example, are different downstream signalling
components expressed in different cell types? Also, how is the cytoskeleton stimulated differently to activate cell migration in one cell
type but inhibit it in another? To begin to answer these questions it is
necessary to understand the mechanisms of activation of receptors and
class B ephrins, the structure ofthese molecules and the pathways which
link the receptors and ephrin-B proteins to the intracellular signalling
cascades.
Understanding the function ofEph signalling in the embryo demands
a knowledge not only of the expression pattern but also the binding
characteristics of the receptor and ligand pair involved. This is because
there are variable affinities of binding within each Eph receptor and
ephrin subclass (Brambilla et al. 1995; Brambilla et al. 1996; Gale et al.
1996; Lackmann et al. 1997; Monschau et al. 1997). This can be best
illustrated with respect to a situation in the embryo where Eph signalling
is known to be involved. One such case is the formation of the retinotectal projection where Eph signalling is required for the formation of the
retinotopic map (Nakamoto et al. 1996). In the mouse, chick and zebrafish two class A ephrins, A2 and A5, are expressed in the tectum with
graded distributions (Brennan et al. 1997; Cheng et al. 1995; Drescher et
al. 1995; see above). In elucidating how the retinotectal map is created it
is important to understand the binding characteristics of these two
ligands with the receptors carried by the projection neurons, the retinal
ganglion cells. One of these receptors is EphA3 and it has been shown
N. Holder et al.
injected with the dominant-negative EphA4 RNA, the forebrain regions
fated to become ventral diencephalon become retina instead and large
expanded eyes are formed. Again, the exact role of EphA4 in the
regionalisation process is unclear, however, since extensive morphogenetic movements underlie the development of eye and ventral diencephalic tissue, an involvement of EphA4 in cell association or
boundary formation is possible.
8.5 Principles of Eph/Ephrin Signalling
Eph receptor/ephrin signalling has been linked to a range of cellular
responses including the control of cell movement, cell shape changes
and cell growth. This raises questions as to how the specificity of
response is achieved. For example, are different downstream signalling
components expressed in different cell types? Also, how is the cytoskeleton stimulated differently to activate cell migration in one cell
type but inhibit it in another? To begin to answer these questions it is
necessary to understand the mechanisms of activation of receptors and
class B ephrins, the structure ofthese molecules and the pathways which
link the receptors and ephrin-B proteins to the intracellular signalling
cascades.
Understanding the function ofEph signalling in the embryo demands
a knowledge not only of the expression pattern but also the binding
characteristics of the receptor and ligand pair involved. This is because
there are variable affinities of binding within each Eph receptor and
ephrin subclass (Brambilla et al. 1995; Brambilla et al. 1996; Gale et al.
1996; Lackmann et al. 1997; Monschau et al. 1997). This can be best
illustrated with respect to a situation in the embryo where Eph signalling
is known to be involved. One such case is the formation of the retinotectal projection where Eph signalling is required for the formation of the
retinotopic map (Nakamoto et al. 1996). In the mouse, chick and zebrafish two class A ephrins, A2 and A5, are expressed in the tectum with
graded distributions (Brennan et al. 1997; Cheng et al. 1995; Drescher et
al. 1995; see above). In elucidating how the retinotectal map is created it
is important to understand the binding characteristics of these two
ligands with the receptors carried by the projection neurons, the retinal
ganglion cells. One of these receptors is EphA3 and it has been shown