THE IDENTIFICATION OF A 9-CIS RETINOL DEHYDROGENASE IN THE MOUSE EMBRYO REVEALS A PATHWAY FOR SYNTHESIS OF 9-CIS RETINOIC ACID

The ligand-controlled retinoic acid (EW) receptors and retinoid X rece ptors are important for several physiological processes, including nor mal embryonic development, but little is known about how their ligands , all-trans and g-cis RA, are generated. Here we report the identifica tion of a stereo-specific 9-cis retinol dehydrogenase, which is abunda ntly expressed in embryonic tissues known to be targets in the retinoi d signaling pathway, The membrane-bound enzyme is a member of the shor t-chain alcohol dehydrogenase/reductase superfamily, able to oxidize 9 -cis retinol into 9-cis retinaldehyde, an intermediate in 9-cis RA bio synthesis. Analysis by nonradioactive in situ hybridization in mouse e mbryos shows that expression of the enzyme is temporally and spatially web controlled during embryogenesis with prominent expression in part s of the developing central nervous system, sensory organs, somites an d myotomes, and several tissues of endodermal origin. The identificati on of this enzyme reveals a pathway in RA biosynthesis, where 9-cis re tinol is generated for subsequent oxidation to 9-cis RA.