Tissue-specific expression of retinoic acid receptor isoform transcripts in the mouse embryo

Abstract

The three murine retinoic acid receptor (RAR) genes each contain two distinct promoters which give rise to protein isoforms differing in their N-terminal regions. This study used in situ hybridization to describe the expression patterns of RARalpha1, RARalpha2, RARbeta1/3, RARbeta2/4, RARgamma1 and RARgamma2 isoform transcripts during mouse embryogenesis. RARalpha1 transcripts are widely distributed, with the exception of the central nervous system. Highest expression is found in developing muscle, pituitary gland and various epithelia. On the other hand, RARalpha2 is essentially expressed along the spinal cord up to the hindbrain 7th rhombomere and in the 4th rhombomere, pons and developing basal ganglia (corpus striatum and pallidum). RARbeta2/4 transcripts account for most of the previously described RARbeta expression features being expressed specifically, or more prominently than RARbeta1/3, in foregut endoderm and its derivatives, olfactory and periocular mesenchyme, urogenital region, proximal limb bud mesenchyme and later within interdigital regions. RARbeta1/3 is more prominently expressed in the developing heart outflow tract mesenchyme, intervertebral disks, midgut loop mesenchyme and umbilical vessel walls. RARbeta1/3 and RARbeta2/4 are coexpressed in the developing corpus striatum. They exhibit, however, distinct dorsoventral distributions along the spinal cord and caudal hindbrain. RARgamma2 is the RARgamma isoform expressed at high levels in the caudal neural groove at embryonic day 8.5. At later stages, both RARgamma isoforms are essentially coexpressed, although the progressive restriction of RARgamma1 transcripts to craniofacial or limb precartilaginous condensations appears to precede that of RARgamma2.

Genetic deletion ofCyp26b1negatively impacts limb skeletogenesis by inhibiting chondrogenesis

“…Quantitative RT-PCR (qPCR) demonstrated that Cyp26b1 is more highly expressed in the distal region of the developing limb bud at E11.5 and E12.5, as previously reported (Pennimpede et al, 2010b;Yashiro et al, 2004) (Fig. 2B) (Mendelsohn et al, 1991;Mollard et al, 2000). Large increases in Rarb expression were observed in To assess retinoid status in the limb mesenchyme, high-density primary limb mesenchymal (PLM) cultures were established from E11.5 wild-type and Cyp26b1 -/-limbs.…”

Retinoic acid signaling in development: Tissue‐specific functions and evolutionary origins

“…These RA reactivity zones are created by localized sources of RA in presumptive fore-and midgut and adjacent mesoderm (established by RALDH1, RALDH2, and RALDH3) combined with specific sinks of RA in the pharynx and organ primordia (such as the lung) (established by CYP26A1, CYP26B1, and CYP26C1) Blentic et al, 2003;MacLean et al, 2001;Reijntjes et al, 2005). In addition, localized endodermal expression of different rar paralogs further fine-tunes this RA signaling activity along the AP axis of the developing endoderm (Bertrand et al, 2007;Mollard et al, 2000). Finally, localized expression of rars in dorsal and ventral areas of the vertebrate endoderm may even create differential RA signaling activities along the dorsoventral (DV) body axis (Pan et al, 2007).…”

Genetic disruption of CYP26B1 severely affects development of neural crest derived head structures, but does not compromise hindbrain patterning

“…RARs form functional heterodimers with the "rexinoid" receptors (RXRs), which bind to specific DNA sequences known as RA response elements (RAREs). There are three distinct RAR genes (␣, ␤, ␥), each with several isoforms that exhibit tissue-specific expression patterns (Dollé et al, 1990;Mollard et al, 2000). However, there is significant functional redundancy amongst the RARs.…”