Eye Development

Abstract

The vertebrate eye comprises tissues from different embryonic origins: the lens and the cornea are derived from the surface ectoderm, but the retina and the epithelial layers of the iris and ciliary body are from the anterior neural plate. The timely action of transcription factors and inductive signals ensure the correct development of the different eye components. Establishing the genetic basis of eye defects in zebrafishes, mouse, and human has been an important tool for the detailed analysis of this complex process. A single eye field forms centrally within the anterior neural plate during gastrulation; it is characterized on the molecular level by the expression of “eye-field transcription factors.” The single eye field is separated into two, forming the optic vesicle and later (under influence of the lens placode) the optic cup. The lens develops from the lens placode (surface ectoderm) under influence of the underlying optic vesicle. Pax6 acts in this phase as master control gene, and genes encoding cytoskeletal proteins, structural proteins, or membrane proteins become activated. The cornea forms from the surface ectoderm, and cells from the periocular mesenchyme migrate into the cornea giving rise for the future cornea stroma. Similarly, the iris and ciliary body form from the optic cup. The outer layer of the optic cup becomes the retinal pigmented epithelium, and the main part of the inner layer of the optic cup forms later the neural retina with six different types of cells including the photoreceptors. The retinal ganglion cells grow toward the optic stalk forming the optic nerve. This review describes the major molecular players and cellular processes during eye development as they are known from frogs, zebrafish, chick, and mice—showing also differences among species and missing links for future research. The relevance to human disorders is one of the major aspects covered throughout the review.

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:

• 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).

• 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.