Chapter Ten - Eye Development
Introduction
The vertebrate eye is a very complex organ (Fig. 10.1) built up by the three major tissues, the cornea, the lens, and the retina. It is obvious that its formation depends on highly organized processes that take place during embryonic development, and mutations in key genes lead to severe congenital disorders. In many vertebrates, the eye is a very prominent organ in the head, and major alterations can be recognized easily. In particular for humans, the eye is one of the most important sensory systems and loss of its function causes many social handicaps and changes in personality. Therefore, the eye has provided a fascinating topic for research since decades.
There are two highlights in eye research, which changed our view fundamentally:
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First of all, at the beginning of the last century Hans Spemann made a careful analysis of eye development: his finding of the dependence of lens induction from the underlying optic cup leads to the discovery of the basic concept of “organizers” in development biology, which became a prototype for tissue interactions in embryonic development (Spemann, 1924).
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Later, thanks to modern genetics, the characterization of causative mutations in congenital human disorders and their comparison to mutations in various model organisms changed a central dogma in zoology, namely the independent evolution of eyes in flies and vertebrates: since the transcription factor Pax6 can induce both, rhabdomeric eyes in Drosophila as well as complex eyes in mammals (Halder et al., 1995), a common genetic network of eye development was suggested first in flies, mice, and humans and included later also frogs and fishes.
However, ongoing research activities revealed also some diversity in eye development among these organisms. This review will focus mainly on eye development in mammals and its key steps, but in some cases it will be compared also to other vertebrates such as Xenopus, zebrafish, or chick.
Section snippets
Overview of Eye Development
During gastrulation, the developing eye is organized as a single field located centrally in the developing forebrain (Adelmann, 1929) (Fig. 10.2). During establishment of the midline, the single “eye field” is separated. During neurulation, two lateral optic pits become apparent as the first signs of the developing eyes. They form when the lateral walls of the diencephalon begin to bulge out (in the mouse at embryonic day 8.5; stage with 11–13 pairs of somites). They enlarge to form half a day
Early Stage: The Eye Field
As mentioned above, the developing eye is organized during gastrulation as a single field located centrally in the developing forebrain. Failure in its formation leads to eyeless phenotypes (anophthalmia). However, if the eye field is formed, but not split into two hemispheres, it results in one single eye, a structure which is named “cyclopia”—a reference to the Cyclops people mentioned by Homer in his epic “Odyssey”; these giants had just one eye in the middle of the forehead.
Formation of the lens placode and Pax6 as its master control gene
Besides the formation of the eye field within the anterior neural plate and its splitting into the future bilateral optic vesicles, the second important step in early eye development is the formation of the lens placode in the surface ectoderm. It starts when the preplacodal region develops in the ectoderm—a transient bilateral structure exhibiting placodal competence leading finally to the anterior pituitary, olfactory neurons, the lens, inner ear, and the trigeminal and epibranchial cranial
The Cornea
Cornea forms as a result of the last series of major inductive events in eye development with the lens vesicle interacting with the overlying surface ectoderm (Fig. 10.6); finally, the cornea consists of an anterior epithelium and a posterior endothelium with the corneal stroma within between. The basis of corneal embryonic development in chick was summarized in great detail by Hay (1979).
During detaching of the lens vesicle from the surface ectoderm, the two tissues remain transiently
The Iris and the Ciliary Body
Whilst the lens and the cornea are being formed, profound changes also occur in the optic cup. The two layers of the optic cup begin to differentiate in distinct directions. The cells of the outer layer produce pigment and eventually form the pigmented layer of the retina, and the inner layer will further differentiate to the neural retina (see below/next section). The area where the developing neural and pigmental retinas meet, the outer lips of the optic cup or the margin of the optic cup, is
The retinal pigmented epithelium
The two layers of the optic cup differentiate (Fig. 10.2): the cells of the outer layer produce pigment and eventually form the RPE. This outer layer is in close contact with the periocular mesenchyme, and signals coming from these cells seem to be important for the further steps to the formation of the RPE. In zebrafish, one of these signaling molecules was identified as activin A, a member of the TGFβ family (Fuhrmann et al., 2000). By contrast, Fgf signaling from the surface ectoderm was
The Optic Nerve
At approximately 47/48 days of gestation (around E11.5 in the mouse), the optic stalk is formed as the connection between the eye and the diencephalon. The axons from the ganglion cells of the inner layer of the retina meet at the base of the eye and travel down to the optic stalk. Initially, the optic stalk represents a narrow neck that connects the optic cup to the diencephalon. Once the axons reach the optic stalk, they grow into it forming the optic nerve (∼E15.5 in the mouse) and relay the
Conclusion and Perspectives
Mutations that lead to clinically relevant phenotypes highlight important steps in eye development: some affect genes that act at the top of the regulatory hierarchy and therefore at the initial stages of eye development, the formation of the eye field. Mutations in these genes (e.g., Pax6, Sox2) lead to anophthalmia, microphthalmia, or aniridia. Other genes (FoxC1, FoxE3, Pitx3, Maf) act downstream or later during development. Some are important just for one particular tissue, for example, the
Acknowledgments
I would like to thank many friends and colleagues who have supported our work within the past years. Unfortunately, due to space limitations I could not refer to all papers dealing with molecular aspects in eye development, and I apologize to those colleagues, who have not been cited.
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