Eph Receptor Tyrosine Kinases and Their Ligands in Development 159
9.4 Formation of Lamina-Specific Synaptic Connections
Beyond their involvement in the topographic projection of sensory
axons, two members of the Eph family, EphrinAS and EphrinB2, have
recently also been implicated in the (non-topographic) processes controlling laminar-specific arborizations (Braisted et al. 1997; Castellani et
al. 1998).
Many parts of the vertebrate central nervous system are divided into
histologically discrete parallel laminae, onto which distinct populations
of afferent axons synapse. These processes appear to be major detenninants of specific connectivity in the central nervous system. The molecular and cellular basis of laminar specificity is largely unknown;
however, besides other molecules (for review see Sanes and Yamagata
1999) some members of the Eph family have been implicated in these
processes. Their activity exclusively in membrane-bound form appears
to fit Eph ligands particularly, in contrast to other, soluble guidance
molecules, for such a function.
In the chick tectum, retinal axons arborize in three different retinorecipient cell layers, that is, layers B, D, and F of the stratum griseum et
fibrosum supeificiale (SGFS). Here, EphrinB2 is expressed restrictively
in layer D and might help guide retinal axons invading the tectum to the
appropriate layers. A number of receptors known to bind EphrinB2 are
expressed in the retina and presumably on retinal ganglion cell axons.
Although its precise function in this patterning process has not been
derennined, EphrinB2 might function either as an attractant for axons
arborizing in layer D or as a repellent for axons projecting into layer B,
thus preventing them from growing into deeper tectallayers (Braisted et
al. 1997).
EphrinAS, on the other hand, is selectively expressed in layer 4 of the
neocortex, whereas one of its receptors, EphAS, is expressed in layers
2/3 and layer S. Backed up by in vitro studies, the function of EphrinAS
in the cortex might be dual: as a branching factor for layer 6 neurons,
which arborize in layer 4, and as a repellent for layer 2/3 neurons, which
connect to layer S and layers 2/3, thus omitting layer 4. The EphA
receptor expressed on layer 6 neurons, possibly mediating the branching
activity, has so far not been identified (Castellani et al. 1998).
Here again, a general principle of axon guidance appears to be in
operation, i.e., that the function of an axon guidance molecule can be
9.4 Formation of Lamina-Specific Synaptic Connections
Beyond their involvement in the topographic projection of sensory
axons, two members of the Eph family, EphrinAS and EphrinB2, have
recently also been implicated in the (non-topographic) processes controlling laminar-specific arborizations (Braisted et al. 1997; Castellani et
al. 1998).
Many parts of the vertebrate central nervous system are divided into
histologically discrete parallel laminae, onto which distinct populations
of afferent axons synapse. These processes appear to be major detenninants of specific connectivity in the central nervous system. The molecular and cellular basis of laminar specificity is largely unknown;
however, besides other molecules (for review see Sanes and Yamagata
1999) some members of the Eph family have been implicated in these
processes. Their activity exclusively in membrane-bound form appears
to fit Eph ligands particularly, in contrast to other, soluble guidance
molecules, for such a function.
In the chick tectum, retinal axons arborize in three different retinorecipient cell layers, that is, layers B, D, and F of the stratum griseum et
fibrosum supeificiale (SGFS). Here, EphrinB2 is expressed restrictively
in layer D and might help guide retinal axons invading the tectum to the
appropriate layers. A number of receptors known to bind EphrinB2 are
expressed in the retina and presumably on retinal ganglion cell axons.
Although its precise function in this patterning process has not been
derennined, EphrinB2 might function either as an attractant for axons
arborizing in layer D or as a repellent for axons projecting into layer B,
thus preventing them from growing into deeper tectallayers (Braisted et
al. 1997).
EphrinAS, on the other hand, is selectively expressed in layer 4 of the
neocortex, whereas one of its receptors, EphAS, is expressed in layers
2/3 and layer S. Backed up by in vitro studies, the function of EphrinAS
in the cortex might be dual: as a branching factor for layer 6 neurons,
which arborize in layer 4, and as a repellent for layer 2/3 neurons, which
connect to layer S and layers 2/3, thus omitting layer 4. The EphA
receptor expressed on layer 6 neurons, possibly mediating the branching
activity, has so far not been identified (Castellani et al. 1998).
Here again, a general principle of axon guidance appears to be in
operation, i.e., that the function of an axon guidance molecule can be