Cell Proliferation and Gene Expression Changes in the Developing Ciliary Body of Otx1-Deficient Mice

Abstract

Abstract: : Purpose:Mice lacking the paired-like homeodomain gene Otx1 display a variety of central nervous system defects as well as malformations of eye structures such as the ciliary body. While much research has been devoted to the study of the brain abnormalities in these mice, the nature of the ciliary body malformation has not been extensively studied. For this reason, we undertook a variety of histological and molecular studies to more completely characterize the ciliary body defects in Otx1-/- mice in both embryonic and adult stages. Methods:We used a combination of histological, cell proliferation and gene expression analyses to characterize the Otx1-/- ciliary body defects. Results: By histological and cell proliferation analysis, we found that development of the ciliary body region in Otx1-/- mice appears to begin normally but that midway through development cell proliferation in the region is reduced, leading to a decrease in ciliary process height. Furthermore, in situ hybridization analyses reveal that two of eight genes normally expressed in the presumptive ciliary body are no longer expressed in the mutant. Conclusion:Our results suggest that Otx1 plays a role in cell proliferation of the ciliary body primordium and in the expression of several genes characteristic of this structure. Interestingly, the gene expression changes do not appear to result from a simple arrest in ciliary body development, as other genes expressed in the presumptive ciliary body at timepoints both earlier and later are not affected by Otx1 loss.

Keywords: 348 ciliary body • 443 in situ hybridization