The genes involved in the morphogenesis of the eye

The two main ways to identify the genes involved in the process of morphogenesis are: 1) to analyze genetic causes in patients or animal models with developmental anomalies and 2) to elucidate patterns of the expression of genes by in situ hybridization during the normal development. In this report, these two methods were adopted to identify the genes involved in the morphogenesis of the eye. A unique mutation of the paired box (Pax)-6 gene (a kind of homeobox gene) was found in a new rat strain "rSey" which showed no induction of both lens and nasal placodes in the homozygote. One base "G" insertion in an exon of the genomic DNA gave rise to a new sequence, "GT", which served as an abnormal 5' splice site to generate an internal deletion in the messenger RNA. The homozygote was also known to have impaired migration of neural crest cells from the anterior midbrain, indicating that the Pax-6 gene would play a role in conducting migration of these neural crest cells. Neural crest-derived mesenchymal cells located around the lens vesicle in the optic cup of mouse embryos were positive for the expression of retinoic acid receptor genes, showing that retinoic acids played a role in the formation of such eye structures composed of neural crest-derived cells as the primary vitreous, corneal, iris, and ciliary stroma. Transcripts of the fibroblast growth factor receptor type 1 were found mainly in neuroepithelium of the optic cup of chick embryos, whereas those of the type 2 receptor were detected in neural crest-derived mesenchymal cells surrounding the optic cup. In contrast, the type 3 receptor was expressed mainly in the lens vesicles, suggesting that altogether 3 types of the fibroblast growth factor receptor would be involved in signaling among different structures as the optic cup, lens vesicle, and neural crest-derived mesenchyme. Receptors for activin, a member of the transforming growth factor beta superfamily, were expressed in the neuroepithelium of the optic cup and in the lens vesicle. In the light of these molecular biological findings, the roles of neural crest-derived cells and epithelial-mesenchymal interactions as well as the concept of positional information in the morphogenesis of the eye were discussed.