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P.H. Mathers, V.A. Voronina, M. Lewandoski; A Continuing Role for the Rx Homeobox Gene in Growth of the Developing Optic Vesicle . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1603.
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Purpose: Loss of expression from the Rx homeobox gene causes a complete loss of retinal development in mice, and mutations in the human RX gene are associated with anophthalmia and microphthalmia. Using mouse genetics, we are interested in studying the functional role that the Rx gene plays in retinal development after the optic vesicle has been formed. Methods: We generated a line of mice that carry a modified allele of the mouse Rx gene, where exon 2 is subject to deletion in the presence of Cre recombinase. We have analyzed mice where the Rx gene is inactivated specifically in the optic vesicle at embryonic day (E)9, a stage when the optic vesicle is rapidly expanding, by expressing Cre under the control of the Foxg1 promoter. Results: Cre-mediated deletion of Rx activity halts the expansion of the optic vesicle as early as E9.5, suggesting a rapid block in retinal stem cell proliferation. Marker analysis within the optic vesicle shows an absence or strong reduction in the expression of several retinal factors, including Pax6, Chx10, Vax2, Six3 and Six6. At the same time, changes in gene expression within the optic stalk are evident, as seen by a shift in Pax2 expression from the stalk to the remaining optic vesicle. By E13, retinal tissue is completely absent from the head, and as a result, newborn pups and adults from these crosses are anophthalmic. Conclusions: Beyond the early requirement for Rx gene expression in the formation of the optic vesicle, these results show that Rx gene activity continues to be necessary to maintain growth of the optic vesicle once established. Our results are consistent with Rx playing a prominent role in controlling the proliferative capacity of early retinal stem cells.
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