Expression of the murine retinol dehydrogenase 10 (Rdh10) gene correlates with many sites of retinoid signalling during embryogenesis and organ differentiation

Abstract

Retinoic acid acts as a signalling molecule regulating many developmental events in vertebrates. As this molecule directly influences gene expression by activating nuclear receptors, its patterns of synthesis have to be tightly regulated, and it is well established that at least three retinaldehyde dehydrogenases (RALDHs) are involved in such tissue-specific synthesis. Whereas embryos from oviparous species can obtain retinaldehyde by metabolizing carotenoids stored in the yolk, placental embryos rely on retinol transferred from the maternal circulation. Here, we show that the gene encoding one of the murine retinol dehydrogenases, Rdh10, is expressed according to complex profiles both during early embryogenesis and organ differentiation. Many of its expression sites correlate with regions of active retinoid signalling and Raldh gene expression, especially with Raldh2 in the early presomitic and somitic mesoderm, retrocardiac and posterior branchial arch region, or later in the pleural mesothelium and kidney cortical region. Rdh10 also shows cell-type and/or regional specificity during development of the palate, teeth, and olfactory system. During limb bud development, it may participate in retinoic acid production in proximal/posterior cells, and eventually in interdigital mesenchyme. These data implicate the retinol to retinaldehyde conversion as the first step in the tissue-specific regulation of retinoic acid synthesis, at least in mammalian embryos. Developmental Dynamics 236:2899 -2908, 2007.

Murine Embryonic Stem Cells Synthesize Retinoic Acid to Promote their Own Differentiation

“…Our findings are consistent with the expression of these enzymes during embryonic development, where ADH3 is detected in mouse pre-implantation embryo [20], and RDH10 and RDH1 in early postimplantation embryo [21][22][23]. RDH10 mutant mice display embryonic lethality at 13.5 d.p.c., and this is the earliest phenotype observed for a single retinol-metabolizing enzyme-deficient mouse [24].…”

Retinol dehydrogenase 10 is a feedback regulator of retinoic acid signalling during axis formation and patterning of the central nervous system

“…A multitude of cytosolic alcohol dehydrogenases and microsomal short-chain dehydrogenases/reductases (SDRs) (Duester et al, 2003;Lidén and Eriksson, 2006), as well as the recently identified CYP1B1 mono-oxygenase (Chambers et al, 2007), can mediate the first step of RA synthesis from vitamin A. Retinol dehydrogenase 10 (RDH10) is a member of the SDR family that oxidizes retinol into retinal (Wu et al, 2002;Wu et al, 2004) in an NAD + -dependent manner (Belyaeva et al, 2008), and exhibits tissue-specific expression at embryonic and foetal mouse stages (Sandell et al, 2007;Cammas et al, 2007;Romand et al, 2008). Analysis of an N-ethyl-N-nitrosourea-generated mutant called trex suggested an essential function of murine RDH10 for RA biosynthesis during limb, craniofacial and organ development (Sandell et al, 2007).…”

The Retinol Dehydrogenase Rdh10 Localizes to Lipid Droplets during Acyl Ester Biosynthesis

“…Rdh10 was identified initially as a visual cycle enzyme (11). Subsequently, Rdh10 was correlated with multiple sites of atRA biosynthesis in the mouse embryo (12). The Rdh10-null mouse is embryonic lethal, and hypomorphs fail to develop a normal cortex, because of decreased but not absent atRA (13)(14)(15)(16).…”