Spatial distributions of retinoic acid receptor gene transcripts in the prenatal mouse inner ear

Abstract

The expression patterns of the three mouse retinoic acid (RA) receptor gene isotypes (RAR␣, RAR␤, and RAR␥) and retinoid X receptor gene isotypes (RXR␣, RXR␤, and RXR␥) have been investigated by in situ hybridization analysis of their RNA transcripts in the inner ear of mouse fetuses at 18.5 days of gestation. Two RARs (RAR␣ and RAR␥) and two RXRs (RXR␣ and RXR␤) presented an almost ubiquitous transcript distribution with overlapping expression in several regions of the cochlea, such as Kölliker's organ, the organ of Corti, the spiral limbus, and nervous structures. The organ of Corti showed an enhanced in situ labeling with RAR␣ and RXR␤. By contrast, RAR␤ and RXR␥ displayed more restricted expression patterns. RXR␥ in particular was strongly expressed in Kölliker's organ and in the spiral ganglion. This expression pattern suggests that RA may be involved in the differentiation of several cochlear cell types. Moreover, the colocalization of several RAR and RXR gene transcripts suggests possible heterodimerization between these receptors in several regions of the cochlea.

Retinoic Acid Repression of Bone Morphogenetic Protein 4 in Inner Ear Development

“…Importantly, by using chicken embryos, we show that the inhibitory effect of at-RA on SCC formation is overcome by exogenous BMP4, indicating that repression of BMP4 lies downstream of at-RA in regulating SCC development. Given that the otocyst expresses RARs (30) and the dehydrogenases necessary to convert vitamin A to at-RA (24, 29), we speculate that at-RA plays a key role in otocyst development via its ability to regulate BMP4 expression directly. at-RA also can affect the otocyst through indirect mechanisms.…”

“…Three genes encode different RAR isotypes (␣, ␤, and ␥). The RARs are expressed in the mouse developing inner ear (30), and mice with combined null mutations of RAR␣ and RAR␥ have abnormal otocyst development (22,39), further supporting an important role for at-RA in the development of this organ.…”

Molecular Signaling in Retinoic Acid-Induced Inner Ear Teratogenesis

“…The expression of RXRγ, by contrast, is much more restricted and is most visible in the spiral ganglion and Kolliker's organ [65]. RXR signal (α, β, γ) is not detected in the otic capsule at these developmental ages.…”

Histone deacetylase inhibition enhances adenoviral vector transduction in inner ear tissue

“…The CMV promoter used in Ad-GFPs contains repeated RAR elements, and these authors concluded that RA may co-operate with TSA on the CMV promoter, with TSA enhancing access to RAR elements by RA. RARs and RXRs are known to be present in the developing sensory epithelia of the inner ear (Romand et al, 1998). Moreover, HCs have been found to be particularly sensitive to the effects of RA (Kelley et al, 1993; Raz and Kelley, 1999).…”