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

TLDR

The study examines the spatial distribution of retinoic acid receptor and binding protein transcripts during early mouse embryogenesis to relate these patterns to segmental gene expression and caudal neuropore maturation. In situ hybridization with 35S‑labeled RNA probes was employed to map transcripts of RAR‑α, β, γ, CRABP I, and CRBP I in mouse embryos during early morphogenesis. CRBP I labels mesenchyme and epiblast during primary mesenchyme formation, CRABP I marks migrating mesenchyme and neural crest cells—most strongly in the preotic hindbrain—while RAR‑β is expressed in presomitic embryos and laterally in the hindbrain, RAR‑α associates with crest cell migration, and RAR‑γ persists in the primitive streak and shifts to the caudal neuropore, supporting the hypothesis that CRABP‑expressing cells are sensitive to excess retinoic acid.

Abstract

ABSTRACT In situ hybridization with 35S-labefled RNA probes was used to study the distribution of transcripts of genes coding for the retinoic acid receptors, RAR-α, βand -γ, 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 preotic hindbrain. RAR-β was present in presomitic stage embryos, being expressed at highest levels in the lateral regions. RAR-α was associated with crest cell emigration and migration, while RAR-γ was present in the primitive streak region throughout the period of neurulation. There was a change from RAR-β to RAR-γ expression at the junction between closed and open neural epithelium at the caudal neuropore. RAR-α and RAR-β 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 pri-mary mesenchyme and neural crest cells, preotic hindbrain), providing further support for our hypoth-esis that cells expressing CRABP are those that cannot tolerate high levels of RA for their normal developmen-tal function.