Altered retinoid signaling in the heads of small eye mouse embryos.

The vitamin A derivative retinoic acid (RA) is necessary for eye development, though its role in signaling within eye tissues is poorly understood. We investigated this question in two transgenic mouse strains carrying a retinoic acid response element (RARE) fused to beta-galactosidase that identify regions of the embryo expressing activated retinoic acid receptors. Retinoid signaling appears in the retina and lens ectoderm of wild-type embryos prior to neural tube closure, when lens induction is under way. To determine if there are interactions between retinoid signaling and the transcription factor Pax-6, also essential for lens development, we examined RARE transgene expression in Small eye (Sey) mice, which carry a Pax-6 mutation. Retinoid signaling in the eye, nose, and forebrain of Sey embryos is decreased, with the most severe effects in the developing lens. In Sey mice the lens anlage cannot respond to exogenous RA after E9, though it is responsive earlier; the retina and other neural ectoderm can respond to RA at any stage. In Sey mice the ability of presumptive lens and retina to produce and/or sequester RA is also decreased, as assayed with a retinoid-reporter cell line. These results implicate retinoid signaling in lens formation and show that RA signaling in the developing eye is dependent upon Pax-6.