Altered retinoid signaling in the heads of small eye mouse embryos

The vitamin A derivative retinoic acid (RA) is necessary for eye developmen t, though its role in signaling within eye tissues is poorly understood. We investigated this question in two transgenic mouse strains carrying a reti noic acid response element (RARE) fused to beta-galactosidase that identify regions of the embryo expressing activated retinoic acid receptors. Retino id signaling appears in the retina and lens ectoderm of wild-type embryos p rior 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 transge ne expression in Small eye (Scy) mice, which carry a Pax-6 mutation. Retino id signaling in the eye, nose, and forebrain of Sey embryos is decreased, w ith the most severe effects in the developing lens. In Sey mice the lens an lage cannot respond to exogenous RA after E9, though it is responsive earli er; 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 sequ ester 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. (C) 2000 Academ ic Press.