Genetic aspects of embryonic eye development in vertebrates

The vertebrate eye comprises tissues from different embryonic origins, e.g., iris and ciliary body are derived from the wall of the diencephalon via optic vesicle and optic cup. Lens and cornea, on the other hand, come from the overlying surface ectoderm. 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 has been an important tool for the detailed analysis of this complex process. One of the main control genes for eye development was discovered by the analysis of the allelic series of the Small eye mouse mutants and characterized as Pax6. It is involved in the interaction between the optic cup and the overlaying ectoderm. The central role for Pax6 in eye development is conserved throughout the animal kingdom as the murine Pax6 gene induces ectopic eyes in transgenic Drosophila despite the obvious diverse organization of the eye in the fruit fly compared to vertebrates. In human, mutations in the PAX6 gene are responsible for aniridia and Peter's anomaly. In addition to Pax6, other mutations affecting the interaction of the optic cup and the lens placode have been documented in the mouse. For the differentiation of the retina from the optic cup several genes are responsible: Mi leads to microphthalmia, if mutated, and encodes for a transcription factor, which is expressed in the melanocytes of the pigmented layer of the retina. In addition, further genes are implicated in the correct development of the retina, e.g., Chx10, Dlx1, GH6, Msx1 and -2, Otx1 and -2, or Wnt7b. Mutations within the retinoblastoma gene (RB1) are responsible for retinal tumors. Knock-out mutants of RB1 exhibit a block of lens differentiation prior to the retinal defect. Besides the influence of Rb1, the lens differentiates under the influence of growth factors (e.g., FGF, IGF, PDGF, TGF), and specific genes become activated encoding cytoskeletal proteins (e.g., filensin, phakinin, vimentin), structural proteins (e.g., crystallins) or membrane proteins (e.g., Mip). The optic nerve originates from the neural retina; ganglion cells grow to the optic stalk, forming the optic nerve. Its retrograde walk to the brain through the rudiment of the optic stalk depends on the correct Pax2 expression.