Retinoic acid in developmental toxicology: Teratogen, morphogen and biomarker

Cyp1B1 expression patterns in the developing chick inner ear

“…It is well accepted that RA generated from the underlying mesenchyme by RALDH activities participate directly in the specification of the neural tube along its anterior‐to‐posterior and dorsal‐to‐ventral axes . Similarly, RA from the periotic mesenchyme may control the regionalization of the developing otic epithelium in a stage‐dependent manner .…”

“…It is well accepted that RA generated from the underlying mesenchyme by RALDH activities participate directly in the specification of the neural tube along its anterior-to-posterior and dorsal-to-ventral axes. 20,39,42,51,54,[110][111][112][113] Similarly, RA from the periotic mesenchyme may control the regionalization of the developing otic epithelium in a stage-dependent manner. 9,10,15,29,107,[114][115][116][117] In the chick, Raldh2 is expressed in the mesoderm caudal to the otic placode, and an appropriate spatial and temporal concentration of the diffusible RA is necessary for the correct specification of the anteriorposterior axis of the developing otic anlagen.…”

“…RA, a small lipophilic signaling molecule, is the main biologically active metabolite of vitamin A (retinol), playing pleiotropic functions during embryonic development . RA biosynthesis occurs in a two‐step process: first, precursor retinol (vitamin A) is oxidized to retinaldehyde by the cytosolic alcohol dehydrogenases and the retinol dehydrogenases; then, retinaldehyde is transformed to RA by members of the aldehyde dehydrogenease class known as retinaldehyde dehydrogenases (RALDH) .…”

“…RA, a small lipophilic signaling molecule, is the main biologically active metabolite of vitamin A (retinol), playing pleiotropic functions during embryonic development. 16,29,[33][34][35][36][37][38][39][40][41][42][43][44][45][46] RA biosynthesis occurs in a two-step process: first, precursor retinol (vitamin A) is oxidized to retinaldehyde by the cytosolic alcohol dehydrogenases and the retinol dehydrogenases; then, retinaldehyde is transformed to RA by members of the aldehyde dehydrogenease class known as retinaldehyde dehydrogenases (RALDH). 16,[47][48][49] The controlling actions of RA occur by regulation of the activity of the RA nuclear receptor family, the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs), to govern the expression of target genes binding to retinoic acid response elements (RAREs) present in the regulatory sequences of these RA-regulated genes.…”

“…37,47,50,51 In addition, RA is degraded by oxidative inactivation by members of the cytochrome P450 family, the sonamed CYP26A-C1 enzymes. [52][53][54] The appropriate distribution of RA within embryonic tissues is determined, therefore, by the balance between its synthesis and its degradation, this being essential for normal development (reviewed in References 29,42,49,52 ).…”