ALCOHOL DEHYDROGENASES IN XENOPUS DEVELOPMENT - CONSERVED EXPRESSION OF ADH1 AND ADH4 IN EPITHELIAL RETINOID TARGET TISSUES

Mammalian alcohol dehydrogenases ADH1 (class I ADH) and ADH4 (class IV ADH) function as retinol dehydrogenases contributing to the synthesis of retinoic acid, the active form of vitamin A involved in growth and development. Xenopus laevis ADH1 and ADH4 genes were isolated using p olymerase chain reaction primers corresponding to conserved motifs of vertebrate ADHs, The predicted amino acid sequence of Xenopus ADH1 was clearly found to be an ortholog of ADH1 from the related amphibian Ra na perezi. Phylogenetic tree analysis of the Xenopus ADH4 sequence sug gested this enzyme is likely to be an ADH4 ortholog, and this classifi cation was more confidently made when based also on the unique express ion patterns of Xenopus ADH1 and ADH4 in several retinoid-responsive e pithelial tissues. Northern blot analysis of Xenopus adult tissues ind icated nonoverlapping patterns of ADH expression, with ADH1 mRNA found in small intestine, large intestine, liver, and mesonephros and ADH4 mRNA found in esophagus, stomach, and skin. These nonoverlapping tissu e-specific patterns are identical to those previously observed for mou se ADH1 and ADH4, thus providing further evidence that Xenopus ADH1 an d ADH4 are orthologs of mouse ADH1 and ADH4, respectively, During Xeno pus embryonic development ADH1 mRNA was first detectable by Northern b lot analysis at stage 35, whereas ADH4 mRNA was undetectable through s tage 47, Whole-mount in situ hybridization indicated that ADH1 express ion was first localized in the pronephros during Xenopus embryogenesis , thus conserved with mouse embryonic ADH1 which is first expressed in the mesonephros. ADH4 expression was not detected in Xenopus embryos by whole-mount in situ hybridization but was localized to the gastric mucosa of the adult stomach, a property shared by mouse ADH4, Conserve d expression of ADH1 and ADH4 in retinoid-responsive epithelial tissue s of amphibians and mammals argue that these enzymes may perform essen tial retinoid signaling functions during development of the pronephros , mesonephros, liver, and lower digestive tract in the case of ADH1 an d in the skin and upper digestive tract in the case of ADH4. Dev. Dyn. 1998;213:261-270. (C) 1998 Wiley-Liss, Inc.