Eph Receptors and Ephrins Are Key Regulators of Morphogenesis 129
and limb muscles, and musck cell lines derived from these different
axial levels inhibit growth of dorsal root ganglion axons to different
extents (Donoghue et al. 1996). These results suggest that specificity in
connections of spinal motor and ganglionic neurons to the periphery
may be based on Eph signalling.
A number of studies have now shown that Eph receptor/ephrin signalling leads to collapse of the neuronal growth cone, resulting in
guidance of axon growth by inhibition. Using the stripe and growth cone
collapse assays developed by Friedrich Bonhoeffer's laboratory it has
been shown that the class A ephrins expressed in mouse, chick and
zebrafish tectum cause growth cone collapse (Brennan et al. 1997;
Drescher et al. 1995; Nakamoto et al. 1996). This is also the case for
chick spinal motor neurons which express EphA4 and EphB2 and which
collapse following interactions with ephrins of the A and B class in in
vitro assays (Henkemeyer et al. 1994; Ohta et al. 1997; Wang and
Anderson 1997).
Observations of growth cone behaviour in cultured eNS neurons
following interactions with ephrins show that they collapse by withdrawal of filopodia (see, for example, Drescher et al. 1995). This has
focused attention on the link between Eph receptor/class B ephrin signalling and the elements of the cytoskeleton. Evidence from in vitro
assays and from targeted mutation studies indicates that signalling via
Eph receptors or class B ephrins can lead to inhibition of growth cone
advance (Henkemeyer et al. 1996). Recent work with cortical neurons in
cu~ture suggests that the responses of their growth cones to class A
versus class B ephrins may be different in terms of the cytoskeletal
components involved (Meima et al. 1997a,b). Interaction with ephrinA5 leads to alterations in actin polymerisation in cortical growth cones
whereas ephrin-Bl does not cause actin rearrangement but appears to
affect microtubules in the growth cone.
8.3 Eph Signalling Is Involved in Controlling Neural Crest
Cell Migration
In the trunk and in the head, neural crest cells take particular paths to
reach the regions of the periphery in which they will settle and differentiate. In the trunk of the rat and chick embryo, for example, crest cells
and limb muscles, and musck cell lines derived from these different
axial levels inhibit growth of dorsal root ganglion axons to different
extents (Donoghue et al. 1996). These results suggest that specificity in
connections of spinal motor and ganglionic neurons to the periphery
may be based on Eph signalling.
A number of studies have now shown that Eph receptor/ephrin signalling leads to collapse of the neuronal growth cone, resulting in
guidance of axon growth by inhibition. Using the stripe and growth cone
collapse assays developed by Friedrich Bonhoeffer's laboratory it has
been shown that the class A ephrins expressed in mouse, chick and
zebrafish tectum cause growth cone collapse (Brennan et al. 1997;
Drescher et al. 1995; Nakamoto et al. 1996). This is also the case for
chick spinal motor neurons which express EphA4 and EphB2 and which
collapse following interactions with ephrins of the A and B class in in
vitro assays (Henkemeyer et al. 1994; Ohta et al. 1997; Wang and
Anderson 1997).
Observations of growth cone behaviour in cultured eNS neurons
following interactions with ephrins show that they collapse by withdrawal of filopodia (see, for example, Drescher et al. 1995). This has
focused attention on the link between Eph receptor/class B ephrin signalling and the elements of the cytoskeleton. Evidence from in vitro
assays and from targeted mutation studies indicates that signalling via
Eph receptors or class B ephrins can lead to inhibition of growth cone
advance (Henkemeyer et al. 1996). Recent work with cortical neurons in
cu~ture suggests that the responses of their growth cones to class A
versus class B ephrins may be different in terms of the cytoskeletal
components involved (Meima et al. 1997a,b). Interaction with ephrinA5 leads to alterations in actin polymerisation in cortical growth cones
whereas ephrin-Bl does not cause actin rearrangement but appears to
affect microtubules in the growth cone.
8.3 Eph Signalling Is Involved in Controlling Neural Crest
Cell Migration
In the trunk and in the head, neural crest cells take particular paths to
reach the regions of the periphery in which they will settle and differentiate. In the trunk of the rat and chick embryo, for example, crest cells