Visual System Development in Vertebrates

Abstract

The development of a functional visual system involves a complex series of inductive and signalling interactions essential for the formation of the eye and its central connections with the brain. Outpouchings from the forebrain, together with the overlying surface ectoderm and neural crest cells give rise to the major structures of the eye (neural retina, pigmented epithelium, lens and cornea). Central connections between the eye and brain regions that receive direct connections from the eye (visual targets) are formed by the axons of retinal ganglion cells. Attractive and repulsive cues in the extracellular environment guide the retinal axon along specific pathways in the brain. Gradients of signalling molecules, together with spontaneous neural activity, drive a point‐to‐point mapping of retinal axons in visual targets, ensuring accurate reconstruction of the visual image. The cellular, molecular and inductive mechanisms that sculpt each of these key developmental processes essential for normal visual system development are beginning to be understood.

Key Concepts:

  • The eye primordia (optic cups) develop as outgrowths from the forebrain.

  • Contact of the optic cup with the overlying surface ectoderm induces formation of the lens.

  • Signals from the lens induce the formation of the cornea.

  • Retinal cells differentiate into overlapping central–peripheral waves to form three layers of cell bodies separated by two plexiform (synaptic) layers.

  • Inhibitory signalling and local adhesive interactions control synaptic specificity in the retina.

  • Attractive and repulsive signals in the extracellular environment direct growth of retinal axons to target regions in the brain.

  • Retinal axons map topographically in target regions of the brain.

  • Map formation is controlled through the graded action of repulsive signalling molecules and spontaneous retinal activity.

  • Activity‐dependent mechanisms drive the formation of eye‐specific layering of synaptic inputs in visual targets.

Keywords: vision; retina; central nervous system; lens induction; axon guidance

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 the photoreceptors synapse with cells in the inner nuclear layer (INL) such as horizontal cells (H) or bipolar cells (B). In the inner nuclear layer are amacrine cells (A) and Mueller glia (Mu). The bipolar cells and inner plexiform cells (I) form synaptic connections with retinal ganglion cells (RGC) in the inner plexiform layer (IPL). RGCs, which have their cell bodies located in the ganglion cell layer (GCL), send their axons along the optic fibre layer (OFL) to the optic disc, where they emerge from the back of the eye in the optic nerve (not shown). Vitreal surface down. Adapted with permission from Dowling . © Association for Research in Vision and Ophthalmology.

Figure 3.

Molecular mechanisms underlying axonal guidance at the optic chiasm of mice. RGC axons expressing Robo receptors exit the retina via the optic nerve. Diffusible Slit molecules delimit a repulsion‐free corridor that demarcates the point where the optic chiasm must form. Axons from the temporal retina (blue lines) that express the EphB1 receptor (induced by the transcription factor Zic2) are repelled by ephrin‐B2 that is expressed by glial cells at the midline. As a consequence of EphB1/ephrin‐B2 interaction, ipsilateral axons turn to project to targets in the same side. Contralateral axons (red lines) do not express EphB1 and ignore Ephrin‐B2. Instead, because they express Neuropilin1 (Nrp1) they are attracted by VEGF‐A expressed at the midline. Additionally, contralateral but not ipsilateral axons express NrCAM and PlexinA1. PlexinA1, NrCAM and Sema6D are also expressed at the midline and interact to help promote midline crossing. Contralateral RGCs express the transcription factor Isl2, although a link between this transcription factor and expression of the crossing axon guidance molecules remains to be established.

Figure 4.

Topographical mapping of retinal axons on to the SC. The retinocollicular connection is highly organised, such that axons from the neighbouring neurons in the retina terminate in neighbouring positions in the SC. Axons originating in the nasal retina terminate in the caudal SC, whereas temporal RGCs send axons to the rostral colliculus. In addition, axons originating in the dorsal retina map to the lateral SC, whereas ventral RGC axons terminate in the medial SC. Retinocollicular mapping is mediated by reciprocal molecular gradients in the retina and SC. 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 SC in an increasing anterior–posterior gradient. Nasal RGC axons project further into the SC because they express fewer EphA receptors and are subsequently less sensitive to the repulsive Ephrin‐A ligands. Conversely, the axons of temporal RGCs invade only a short distance into the SC because of their high sensitivity to Ephrin‐A ligands. In the dorsoventral axis, a gradient of EphB receptors exists in the retina with highest expression ventrally, while a gradient of Ephrin‐B, highest medially, is expressed in the colliculus. In this case, however, EphB/ephrin‐B signalling seems to mediate attraction.

Figure 5.

Diagram of the retinogeniculocortical projection in primates. (a) An outline of the pathway, going from the retina (top) through the optic chiasm to the lateral geniculate nucleus (LGN). Second relay neurons in the LGN project to layer 4 of the primary visual cortex, maintaining a rough topographical map of the visual world. (b) Projections from the retina to the LGN. 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.. © McGraw‐Hill.

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Further Reading

Adler R and Canto‐Soler MV (2007) Molecular mechanisms of optic vesicle development: complexities, ambiguities and controversies. Developmental Biology 305: 1–13.

Donner AL , Lachke SA and Maas RL (2006) Lens induction in vertebrates: variations on a conserved theme of signaling events. Seminars in Cell and Developmental Biology 17: 676–685.

Erskine L and Herrera E (2007) The retinal ganglion cell axon's journey: insights into molecular mechanisms of axon guidance. Developmental Biology 308: 1–14.

Gilbert SF (2010) Developmental Biology, 9th edn, Sunderland, MA, USA: Sinauer Associates Inc.

Harada T , Harada C and Parada LF (2007) Molecular regulation of visual system development: more than meets the eye. Genes and Development 21: 367–378.

Kandel ER , Schwartz JH , Jessell TM , Siegelbaum SA and Hudspeth AJ (2012) Principles of Neural Science, 5th edn, New York, USA: McGraw‐Hill Medical.

Petros TJ , Rebsam A and Mason CA (2008) Retinal axon growth at the optic chiasm: to cross or not to cross. Annual Review of Neuroscience 31: 295–315.

Price D , Jarman AP , Mason JO and Kind PC (2011) Building Brains: An Introduction to Neural Development, 1st edn. Chichester, West Susses, UK: Wiley‐Blackwell.

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Herrera, Eloisa, and Erskine, Lynda(Sep 2013) Visual System Development in Vertebrates. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000789.pub3]