Aldehyde dehydrogenases in the generation of retinoic acid in the developing vertebrate: a central role of the eye.

In the developing vertebrate, retinoic acid is distributed in patterns that are highly regulated, both in the spatial and temporal domains. These patterns are generated by the localized expression of retinoic acid-synthesizing aldehyde dehydrogenases, which form the origins of retinoic acid-diffusion gradients in the surrounding tissues. The developing eye, known to be exceptionally vulnerable to vitamin A deficiency, is one of the retinoic acid-richest regions in the embryo. Several aldehyde dehydrogenases are expressed here, and they create a ventro-dorsal retinoic acid gradient in the embryonic retina. Aldehyde dehydrogenase expression persists in the mature eye and is stable, but the amount of retinoic acid synthesized is variable, depending on ambient light levels. This phenomenon is due to changing levels of the retinoic acid precursor retinaldehyde, which is released from illuminated rhodopsin, thus providing a mechanism by which light can directly influence gene expression. For arrestin mRNA, which is one of the factors known to be regulated by light, the light effect can be mimicked in the dark by injection of retinoic acid. The light-induced release of retinaldehyde from rhodopsin, which occurs only in vertebrate but not invertebrate photoreceptors, may have accelerated the rapid evolution of retinoic acid-mediated transcriptional regulation at the transition from invertebrates to vertebrates, and it may explain the prominent role of retinoic acid in the eye.