Figure 1

Chemical labelling system in retinocollicular map in mice A. Formation of the map in the wild-type mouse. Retinal ganglion cells (RGC) express EphA5/6 receptors in temporal > nasal gradient (bottom), whereas the cells in SC express the ephrin-A ligands in caudal > rostral gradient (top). Since axons of Eph+ RGC (red arrows) are repelled by ephrins this distribution of chemical markers leads to establishing of ordered topographic map in which nasal/temporal retina projects to caudal/rostral SC. This is because RGC axons expressing highest levels of Eph receptors (temporal) experience the largest repulsion and are expelled to the rostral part of SC, where such repulsion is minimal. Axons of nasal RGC are more indifferent to the action of ligands and occupy more caudal positions. Such system allows positioning of RGC axons in the order of increasing expression level of EphA receptors. B. Map in the mutant mouse from Ref. [20]. The expression level of EphA receptors was artificially increased in every second cell by genetic manipulations (dark gray). This is done by co expressing EphA3, which is absent in the wild-type RGCs (see A), with another gene, Isl2, which is expressed roughly in 50% of RGCs. Since ephrin ligands bind and activate all receptors from EphA family, albeit with different affinity, this results in anomalous projection to SC, based roughly on the total levels of EphA in each axon. Similarly to A this leads to sorting of axons in the order of increasing density of EphAs (red arrows). Note that two RGC neighboring in retina become separated in SC (bold arrows). This aberration in the topographic map leads to two termination zones (TZs) in SC for two neighboring cells in retina, rather than a single zone in wild-type [20].