Figure 1. Development of the vertebrate eye. (a) The lateral neuroepithelium evaginates towards the overlying presumptive lens ectoderm, creating an optic vesicle. (b) When this bulge contacts the overlying ectoderm, it begins to invaginate, while the overlying ectoderm thickens to form a lens placode. (c) Progressive invagination of the neuroepithelium generates the optic cup. (d) while the invaginating lens placode forms the lens pit. The presumptive lens tissue eventually buds off from the overlying epithelium to form a lens vesicle, and the neuroepithelium behind the optic cup constricts to form the optic stalk. (e) Differentiation of the neural retina then takes place, and the pigmented epithelium forms around the retina. Axons from retinal ganglion cells at the innermost surface of the retina exit the eye on their way to the brain, forming the optic nerve.

Figure 2. Diagram of a section through the vertebrate neural retina. At the top are the photoreceptors (R) in the outer nuclear layer (ONL). Below this is the outer plexiform layer (OPL) where photoreceptors synapse with cells in the inner nuclear layer (INL) such as horizontal cells (H) or bipolar cells (B). Also in the inner nuclear layer are amacrine cells (A) and Mueller glia (Mu). Bipolar cells and inner plexiform cells (I) form synaptic connections with retinal ganglion cells (RGC) in the inner plexiform layer (IPL). RGCs send their axons along the optic fibre layer (OFL) to the optic nerve head, where they emerge from the back of the eye in the optic nerve (not shown). Adapted with permission from Dowling JE (1970) Organization of vertebrate retimes. Investigative Ophthalmology 9: 655–680.

Figure 3. Topographical mapping of retinal axons on to tectal targets. The retinotectal connection is highly organized, such that axons from neighbouring neurons in the retina terminate in neighbouring positions in the tectum. Axons originating in the nasal retina terminate in the posterior tectum, while temporal RGCs send axons to the anterior tectum. In addition, axons originating in the dorsal retina map to the ventral tectum, while ventral RGC axons terminate in the dorsal tectum. Retinotectal mapping is mediated by reciprocal molecular gradients in the retina and tectum. EphA receptors are expressed by RGCs in an increasing nasal-temporal gradient. Nasal neurons express few EphA receptors, whereas neurons located more temporally express progressively more receptors. Ephrin-A ligands, which inhibit RGC elongation, are expressed in the tectum in an increasing anterior–posterior gradient. Nasal RGC axons project further into the tectum because they express fewer EphA receptors and are subsequently less sensitive to the repulsive Ephrin-A ligands. Conversely, the axons of temporal RGCs can invade only a short distance into the tectum because of their high sensitivity to the Ephrin-A ligands. In the dorsoventral axis, a gradient of Ephrin-B ligands exists in the retina with highest expression dorsally, while a gradient of EphB receptors, highest ventrally, is expressed in the tectum. In this case, however, axon guidance is established by growth cone attraction of Ephrin-B-expressing axons to EphB receptors in the tectum. Thus, dorsal RGCs project axons to the ventral tectum while ventral RGCs project to the dorsal tectum, and reverse signalling mediated by Ephrin-B ligands on the retinal growth cones underlies topographical mapping in the dorsoventral axis. A, anterior; P, posterior; N, nasal; T, temporal; D, dorsal; V, ventral.

Figure 4. Diagram of the retinogeniculocortical projection in primates. (a) An outline of the pathway, going from the retinae (top) through the optic chiasm to the lateral geniculate nucleus (LGN; shown in (b)). The LGN then projects to layer 4 of the primary visual cortex (shown in (c)), maintaining a rough topographical map of the visual world. (b) Projections from the retinae to the LGN. Note that retinal ganglion cells project to eye-specific layers within the LGN. Axons from the nasal half of the contralateral eye (C) project to layers 1C, 4C and 6C, whereas temporal axons from the ipsilateral eye project to layers 2I, 3I and 5I. (c) Structure of hypercolumns in the primary visual cortex. LGN inputs arrive in layer 4, where they are segregated into ocular dominance columns, blobs and orientation-selective columns. Adapted from Kandel et al. (1991) Principles of Neural Science, 3rd edn. East Norwalk, CT: Appleton and Lange, with permission from The McGraw-Hill Companies.