Retinoic acid receptors and cellular retinoid binding proteins : II. Their differential pattern of transcription during early morphogenesis in mouse embryos

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Abstract

In situ hybridization with 35S-labelled RNA probes was used to study the distribution of transcripts of genes coding for the retinoic acid receptors, RAR-alpha, -beta and -gamma, and the cellular binding proteins for retinoic acid (CRABP I) and retinol (CRBP I), in mouse embryos during the period of early morphogenesis. Primary mesenchyme formation was associated with CRBP I labelling of both epiblast and mesenchyme of the primitive streak, while the CRABP probe labelled the migrating primary mesenchyme cells. Neural crest cell emigration and migration were associated with CRABP labelling of both neural epithelium (excluding the floor plate) and neural crest cells, while CRBP I expression was restricted to basal and apical regions of the epithelium (excluding the floor plate). The strongest neuroepithelial signal for CRABP was in the preoptic hindbrain. RAR-beta was present in presomitic stage embryos, being expressed at highest levels in the lateral regions. RAR-alpha was associated with crest cell emigration and migration, while RAR-gamma was present in the primitive streak region throughout the period of neurulation. There was a change from RAR-beta to RAR-gamma expression at the junction between closed and open neural epithelium at the caudal neuropore. RAR-alpha and RAR-beta were expressed at specific levels of the hindbrain and in the spinal cord. These distribution patterns are discussed in relation to segmental expression patterns of other genes, and to maturational changes in the caudal neuropore region. The CRABP transcript distribution patterns correlated well with known target tissues of excess retinoid-induced teratogenesis (migrating primary mesenchyme and neural crest cells, preoptic hindbrain), providing further support for our hypothesis that cells expressing CRABP are those that cannot tolerate high levels of RA for their normal developmental function.

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