The requirement of pax6 for postnatal eye development: evidence from experimental mouse chimeras.

PURPOSE: The small eye mouse mutant (Sey) is caused by a mutation of the Pax6 gene. Previous studies, in which aggregation chimeras were used, have demonstrated that Sey/Sey cells contribute poorly to the neural retina forming small clumps of cells restricted to the inner retina at embryonic day 16.5. In addition, Sey/+ cells are absent from the lens epithelium during this embryonic period and postnatally. This study was conducted to determine the fates of these Sey/Sey and Sey/+ cells with continued development in chimeric mouse eyes.

METHODS: Observations were made on heterozygous and homozygous Sey cells in chimeric eyes from postnatal day (P)0 to P10.

RESULTS: In Sey/Sey<-->wild-type (wt) chimeras, all Sey/Sey cells originating from retinal progenitor cells died at perinatal times. The only remaining Sey/Sey cells in the neural retina were associated with blood vessels, including vascular endothelial cells, pericytes, astrocytes, and microglia, which have extraretinal origins. In contrast, Sey/+ cells formed all retinal cell classes. As previously reported, Sey/Sey cells were absent from the lens and corneal epithelium. However, in contrast to previous reports, Sey/+ cells contributed to the lens epithelium as well as corneal tissues, and Sey/Sey cells were absent from the anterior retinal pigment epithelium.

CONCLUSIONS: All evidence showed that, when Pax6 is absent at the initial stages of the development, Sey/Sey cells that contribute to the neural retina die, even when wild-type cells are available to provide normal environmental cues.