The requirement of vitamin A (retinol) for successful completion of vertebrate embryogenesis is well established. Retinoid signaling involves a two‐step metabolic event in which retinol is first converted to retinal, and then retinal is converted to the active ligand retinoic acid, which modulates the transcriptional activity of a nuclear retinoic acid receptor (RAR). During mouse embryogenesis, retinoic acid is not detected at 6.5 days of embryonic development (E6.5) when gastrulation first initiates, but it is detected at E7.5 and later. This suggests that retinoid signaling during embryo‐genesis may be initiated during the primitive streak stage. Here we have used whole‐mount in situ hybridization to examine E6.5–E8.5 mouse embryos for expression of RARα, RARβ, RARγ, and two enzymes, class IV alcohol dehydrogenase (ADH‐IV) and class I aldehyde dehydrogenase (ALDH‐I), which have been shown to have retinol and retinal dehydrogenase activities, respectively. At E6.5, RARα mRNA was expressed ubiquitously in embryonic and extraembryonic tissues, RARγ mRNA was detected throughout all embryonic tissues, but mRNAs for RARβ, ADH‐IV, and ALDH‐I were not detected. By E7.5, RARα mRNA was still ubiquitous, RARβ mRNA was now observed in presumptive hindbrain ectoderm and adjacent mesenchyme, RARγ mRNA was still observed in all embryonic tissues, and ADH‐IV as well as ALDH‐I mRNAs were now both expressed in primitive streak mesoderm. In E8.5 embryos, RARα mRNA was still ubiquitous, RARβ mRNA was present in the caudal hindbrain as well as the closed neural tube and foregut, RARγ mRNA was widespread but most prevalent in caudal embryonic tissues, and mRNAs for both ADH‐IV and ALDH‐I were expressed in cranial mesenchyme, somites, and paraxial mesoderm. Thus, ADH‐IV and ALDH‐I, two metabolic enzymes able to convert retinol to retinoic acid, are both initially expressed in primitive streak mesoderm at E7.5 when retinoic acid is first detectable. On the other hand, RARα and RARγ expression is widespread and present at E6.5 prior to retinoic acid detection. These results suggest that upregulation of ADH‐IV and ALDH‐I gene expression in primitive streak mesoderm may lead to retinoic acid synthesis and initiation of retinoid signaling during mouse embryogenesis. Dev. Dyn. 208:536–543, 1997. © 1997 Wiley‐Liss, Inc.
Developmental Dynamics – Wiley
Published: Apr 1, 1997
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