128
N. Holder et al.
carrying a mutation in the ephrin-A5 gene has abnormal projections of
retinal ganglion cells to the tectum (Frisen et al. 1998). Although the
gross aspects of the topographic map are normal in these mutants, axons
that normally project to the caudal end of the tectum grow into the
hindbrain region in the mutants. This result indicates that ephrin-A5 acts
primarily as a block to axon growth. It is, however, not clear that all
vertebrates will pattern the retinotectal projection in quite the same way.
In the zebrafish, for example, there are three ligands present in the
tectum, two of which have been shown to possess axon growth inhibitory properties (Brennan et al. 1997) and the zebrafish EphA4 homologue is absent from the eye (Xu et al. 1996).
The visual system is a complex of different axonal pathways and
targets and it appears that some Eph receptors are involved in controlling the growth of specific subsets of these axonal projections. This has
been demonstrated by the targeted mutation of the mouse EphA8 gene,
which is normally expressed in a rostro-caudal gradient in the eye and in
the superior colliculus. Mutant animals lack normal contralateral connections between the superior colliculi as well as connections from the
superior colliculus to the spinal cord (Park et al. 1997).
The formation of topographic maps is not limited to the visual system
and is a feature of other regions of the eNS such as the hippocampus
and septum which are areas involved in learning and memory. It has
been shown that an Eph signalling system may underlie the formation of
topographic projections involving the septum and hippocampus (Gao et
al. 1996; Zhang et al. 1996). The hippocampal neurons project to the
lateral septum in a precise order and the hippocampus receives input
from the medial septum. Ephrin-A2 is expressed in a dorsal-to-ventral
gradient in the septum and, in culture, selectively allows growth of
axons from appropriate regions of the hippocampus. The receptor
EphA5, is expressed in a complementary lateral-to-medial gradient in
the hippocampus.
Gene expression patterns suggest that Eph receptor signalling may be
involved in establishing specific neuronal connections in the developing
peripheral nervous system too. For example, the mouse receptor EphA3,
and its rat and chick homologues are expressed in a subset of spinal
motor neurons and a subset of axial muscles (Kilpatrick et al. 1996;
Ohta et al. 1996). Furthermore, in the mouse, the ligand ephrin-A5 is
expressed to a greater extent by head and neck muscles than by trunk
N. Holder et al.
carrying a mutation in the ephrin-A5 gene has abnormal projections of
retinal ganglion cells to the tectum (Frisen et al. 1998). Although the
gross aspects of the topographic map are normal in these mutants, axons
that normally project to the caudal end of the tectum grow into the
hindbrain region in the mutants. This result indicates that ephrin-A5 acts
primarily as a block to axon growth. It is, however, not clear that all
vertebrates will pattern the retinotectal projection in quite the same way.
In the zebrafish, for example, there are three ligands present in the
tectum, two of which have been shown to possess axon growth inhibitory properties (Brennan et al. 1997) and the zebrafish EphA4 homologue is absent from the eye (Xu et al. 1996).
The visual system is a complex of different axonal pathways and
targets and it appears that some Eph receptors are involved in controlling the growth of specific subsets of these axonal projections. This has
been demonstrated by the targeted mutation of the mouse EphA8 gene,
which is normally expressed in a rostro-caudal gradient in the eye and in
the superior colliculus. Mutant animals lack normal contralateral connections between the superior colliculi as well as connections from the
superior colliculus to the spinal cord (Park et al. 1997).
The formation of topographic maps is not limited to the visual system
and is a feature of other regions of the eNS such as the hippocampus
and septum which are areas involved in learning and memory. It has
been shown that an Eph signalling system may underlie the formation of
topographic projections involving the septum and hippocampus (Gao et
al. 1996; Zhang et al. 1996). The hippocampal neurons project to the
lateral septum in a precise order and the hippocampus receives input
from the medial septum. Ephrin-A2 is expressed in a dorsal-to-ventral
gradient in the septum and, in culture, selectively allows growth of
axons from appropriate regions of the hippocampus. The receptor
EphA5, is expressed in a complementary lateral-to-medial gradient in
the hippocampus.
Gene expression patterns suggest that Eph receptor signalling may be
involved in establishing specific neuronal connections in the developing
peripheral nervous system too. For example, the mouse receptor EphA3,
and its rat and chick homologues are expressed in a subset of spinal
motor neurons and a subset of axial muscles (Kilpatrick et al. 1996;
Ohta et al. 1996). Furthermore, in the mouse, the ligand ephrin-A5 is
expressed to a greater extent by head and neck muscles than by trunk