Spatial and temporal pattern of expression of the cellular retinoic acid-binding protein and the cellular retinol-binding protein during mouse embryogenesis.

The Adh-1 gene product, ADH-A2, the only known murine class I alcohol dehydrogenase, is able to oxidize retinol (vitamin A) into retinaldehyde, the first enzymatic step in the conversion of retinol into its biologically active metabolite retinoic acid. We have investigated the developmental expression pattern of Adh-1 transcripts by in situ hybridization. Transcripts were first detected by embryonic day 10.5 in the mesonephros mesenchyme. During the following gestational days, Adh-1 transcripts were detected in several mesenchymal areas, such as nasal, laterocervical, and genital regions. Adh-1 transcripts were also detected in a small ectodermal domain at the anterior margins of both forelimbs and hindlimbs. During late fetal development, Adh-1 transcripts were found essentially in the epidermis and in a number of tissues which continue to express the gene after birth, such as liver, kidney, gut epithelium, adrenal cortex, testis interstitium, and ovarian stroma. In contrast, a strong expression of Adh-1 was found in the mesenchyme of developing lungs, but not in the adult organ. This highly regulated expression of Adh-1 is discussed with respect to the local synthesis of retinoic acid during development. Although the promoter of the human counterpart of Adh-1 contains a retinoic acid response element (Duester et al. 119913 Mol. Cell. Biol. 11:1638-1646), we report that this element is not conserved in the murine gene. Consistently, Adh-1 promoter-containing reporter constructs were not retinoic acid-inducible in cotransfections assays with RARs and/or RXRs, suggesting that retinoic acid regulation of Adh-1 differs from that of the human gene.

Section: Discussionmentioning

confidence: 99%

Stage and tissue‐specific expression of the alcohol dehydrogenase 1 (Adh‐1) gene during mouse development

Vonesch

Nakshatri

Philippe

et al. 1994

“…Previous descriptions of the expression patterns of CRABP-I (Dolle et al, 1989;Perez-Castro et al, 1989;Ruberte et al, 1991Ruberte et al, , 1992Maden et al, 1992) and CRABP-I1 during early mouse morphogenesis have relied on in situ hybridization of sectioned untreated embryos. We performed wholemount in situ hybridization of mouse embryos from 7.5 to 9.5 days postcoitum (E7.5-9.5) to further investigate the normal patterns of expression of CRABP-I and CRABP-I1 and the effects of exogenous RA on the distribution of CRABP-I and -11 transcripts during development.…”

Section: Whole-mount In Situ Hybridization Analysismentioning

confidence: 99%

Localization of CRABP‐I and CRABP‐II mRNA in the early mouse embryo by whole‐mount in situ hybridization: Implications for teratogenesis and neural development

Lyn

Giguère

1994

Retinoic acid (RA) has been implicated in vertebrate neural pattern formation. In this paper we analysed the expression patterns of the cellular retinoic acid binding proteins (CRABP‐I and II) during early morphogenesis in normal and RA‐treated mouse embryos by whole‐mount in situ hybridization. This technique allowed a detailed analysis of the spatial and temporal changes in mRNA expression pattern. Both CRABPs were expressed in a rhombomere specific pattern; putative neural crest cells in the branchial arches expressed the CRABPs at levels corresponding to the rhombomere from which they were derived. CRABP‐II, but not CRABP‐I, was expressed in the neural epithelium caudal to the hindbrain. CRABP‐I is strongly expressed in a fine net‐like pattern which extends from the caudal diencephalon to the rostral hindbrain and remains predominantly dorsal to the lateral midline of the neural tube. This network corresponds to the pattern formed by the putative first axons of the embryonic mouse brain which are produced by the developing neurons of the mesencephalic nucleus of the trigeminal nerve. Although the expression of CRABP‐I was unaffected by a teratogenic dose of RA, CRABP‐II expression was increased slightly with no alteration in the normal spatial or temporal boundaries. These results support the suggestion that the CRABPs may play an important role in modulating endogenous RA levels, particularly in the developing nervous system and its neural crest derivatives. Furthermore, the limited ability of CRABP mRNA levels to respond to exogenous retinoids may be a factor in retinoid teratogenicity. © 1994 Wiley‐Liss, Inc.

“…Based upon data showing its ubiquitous expression in animals (Kato et al, 1985) and the feature of its promoter sequence (Wei et al, 1990), this gene has been characterized as a housekeeping gene. Nevertheless, it has been shown to be expressed at very high levels during embryonic stages (Dolle et al, 1990;Perez-Castro et al, 1989;Wei et al, 1991). In mouse embryonal carcinoma cell line P19, in which cellular differentiation can be induced by RA, CRABP-I gene is specifically upregulated by RA .…”

mentioning

confidence: 99%

Demethylation in the 5′‐flanking region of mouse cellular retinoic acid binding protein‐I gene is associated with its high level of expression in mouse embryos and facilitates its induction by retinoic acid in P19 embryonal carcinoma cells

Wei

Lee

1994

The mouse cellular retinoic acid binding protein-I (CRABP-I) gene is specifically up-regulated by retinoic acid (RA) in P19 mouse embryonal carcinoma cells, and its expression in animals is spatially and temporally restricted to RA-sensitive tissues during embryonic development. This study demonstrates that, in adult mouse tissues and P19 cells where the expression of CRABP-I is detected at the basal level, the 5'-flanking region of the CRABP-I gene is hypermethylated at the C residues of all the H p a I1 sites. Conversely, in mouse embryos during early stages of development when the expression of CRABP-I gene is detected at a much higher level, this region is demethylated at these H p a I1 sites. In P19, enhancement on the RA-induced up-regulation of CRABP-I can be observed in cells treated with 5-azacytidine (5-AzaC) in conjunction with RA, where partial demethylation in the 5'-flanking region of CRABP-I gene is observed. Nuclear run-on experiments indicate that increased message levels of CRABP-I in P19 cells can be accounted for, at least partially, by increases in its transcription rates. The induction of retinoic acid receptor (RAR) p by RA can also be enhanced by 5-AzaC, but to a much lesser degree. In contrast, all the H p a I1 sites in the structural gene portion, at least in the first two exons, are fully demethylated at the C residues. o 1994 WiIey-Liss, Inc.