Retinoic acid (RA) signaling is a central pathway regulating anterior-posterior patterning of the embryo through its targets, the Hox genes. RA is produced by two sequential oxidations from vitamin A (retinol) and this biosynthesis has to be regulated temporally, spatially and quantitatively. Mining Xenopus embryonic expression databases identified a novel component of the RA metabolic network, ADHFe1. Using Xenopus laevis embryos as our experimental system we determined the temporal and spatial pattern of AdhFe1 expression. Gain- and loss-of-function of ADHFe1 were induced to study its function and the regulation of the AdhFe1 gene by RA was studied. Expression analysis localized the ADHFe1 protein to the late Spemann's organizer, the trunk organizer. Subsequently, ADHFe1 can be detected in the prechordal mesoderm, the notochord and the lateral plate mesoderm. Manipulation of ADHFe1 levels affects the normal Hox gene expression. The effects of ADHFe1 manipulation can by rescued by increasing the levels of RA or its biosynthesis. Expression of the AdhFe1 gene is regulated by RA itself. ADHFe1 is an enzyme active already during gastrula stages and the protein is still present during neurula stages. ADHFe1 regulates the expression of the Hox genes during the early patterning of the trunk. The effect of ADHFe1 on Hox expression is mediated through regulation of RA levels. ADHFe1 probably reduces retinaldehyde to retinol thereby restricting the availability of retinaldehyde, the substrate needed by retinaldehyde dehydrogenases to produce RA making it a novel regulator of RA concentrations in the embryo and RA homeostasis.

Intrauterine growth restriction (IUGR) is commonly observed in human pregnancies and can result in severe clinical outcomes. IUGR is observed in Fetal Alcohol Syndrome (FAS) fetuses as a result of alcohol (ethanol) exposure during pregnancy. To further understand FAS, the severe form of Fetal Alcohol Spectrum Disorder, we performed an extensive quantitative analysis of the effects of ethanol on embryo size utilizing our Xenopus model. Ethanol-treated embryos exhibited size reduction along the anterior-posterior axis. This effect was evident primarily from the hindbrain caudally, while rostral regions appeared refractive to ethanol-induced size changes, also known as asymmetric IUGR. Interestingly, some embryo batches in addition to shortening from the hindbrain caudally also exhibited an alcohol-dependent reduction of the anterior head domain, known as symmetric IUGR. To study the connection between ethanol exposure and reduced retinoic acid levels we treated embryos with the retinaldehyde dehydrogenase inhibitors, DEAB and citral. Inhibition of retinoic acid biosynthesis recapitulated the growth defects induced by ethanol affecting mainly axial elongation from the hindbrain caudally.To study the competition between ethanol clearance and retinoic acid biosynthesis we demonstrated that, co-exposure to alcohol reduces the teratogenic effects of treatment with retinol (vitamin A), the retinoic acid precursor. These results further support the role of retinoic acid in the regulation of axial elongation.