Brain structures of a medaka mutant, el (eyeless), in which eye vesicles do not evaginate

Eye development and brain structures of a mutant teleost fish were investigated. The el (eyeless) mutation in medaka (Oryzias latipes) is recessive and affects eye formation; in the most severe cases, it results in the absence of eyes. Developmental studies revealed that normal eyeballs are not formed in the el mutant embryos, but small optic cup-like structures differentiate in situ in the walls of the prosencephalon without evagination. The anophthalmic el homozygous fish hatched normally, although they did not respond behaviorally to visual stimuli. A small fraction of these fish grew to adulthood. In the adult anophthalmic el homozygous fish, the brain exhibited abnormalities in several subdivisions. A pair of small abnormal protrusions was observed on the surface of the ventral telencephalon and preoptic area. Immunocytochemistry using a rhodopsin monoclonal antibody showed that opsin-positive cells were present in the abnormal structures. Bodian staining showed that the optic nerves were present near the abnormal structures, although the number of optic nerve fibers was extremely small. The optic tectum was extremely small, and the thickness of the stratum opticum and stratum fibrosum et griseum superficiale was reduced. These behavioral and morphological observations suggest that the adult anophthalmic el homozygous fish are functionally blind, although small retina-like structures were partially differentiated and persisted in the adult fish brain. Moreover, the adult anophthalmic el homozygous fish were infertile, and the sizes of the hypophysis and the hypothalamus were reduced. Thus, the el mutation affects not only the brain structures that are related to the visual system but also those related to the reproductive system.