Endogenous Status of Retinoids and Their Cytosolic Binding Proteins in Limb Buds of Chick vs Mouse Embryos

Scott, William J.; Walter, Rosemarie; Tzimas, Georg; Sass, Jörn Oliver; Nau, Heinz; Collins, Michael D.

doi:10.1006/dbio.1994.1262

Cited by 60 publications

(33 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…HPLC has been used to detect all-trans-RA and all-transretinol in the mouse embryo (Satre & Kochhar, 1989;Scott et al 1994;, and in the chick embryo the didehydroretinoids have also been detected (Thaller & Eichele, 1990;Scott et al 1994;Dong & Zile, 1995;Maden et al 1998b). Xenopus and zebrafish (Danio rario) embryos also contain a variety of retinoids (Durston et al 1989;Pijnappel et al 1993;Creech-Kraft et al 1994;Costaridis et al 1996).…”

Section: Endogenous Retinoic Acidmentioning

confidence: 99%

The role of retinoic acid in embryonic and post-embryonic development

Maden

2000

Proc. Nutr. Soc.

116

View full text Add to dashboard Cite

Retinoic acid (RA) is the bioactive metabolite of vitamin A (retinol) which acts on cells to establish or change the pattern of gene activity. Retinol is converted to RA by the action of two types of enzyme, retinol dehydrogenases and retinal dehydrogenases. In the nucleus RA acts as a ligand to activate two families of transcription factors, the RA receptors (RAR) and the retinoid X receptors (RXR) which heterodimerize and bind to the upstream sequences of RA-responsive genes. Thus, in addition to the well-established experimental paradigm of depriving animals of vitamin A to determine the role of RA in embryonic and post-embryonic development, molecular biology has provided us with two additional methodologies: knockout the enzymes or the RAR and RXR in the mouse embryo. The distribution of the enzymes and receptors, and recent experiments to determine the endogenous distribution of RA in the embryo are described here, as well as the effects on the embryo of knocking out the enzymes and receptors. In addition, recent studies using the classical vitamin A-deprivation technique are described, as they have provided novel insights into the regions of the embryo which crucially require RA, and the gene pathways involved in their development. Finally, the post-embryonic or regenerating systems in which RA plays a part are described, i.e. the regenerating limb, lung regeneration, hair cell regeneration in the ear and spinal cord regeneration in the adult.

show abstract

Section: Endogenous Retinoic Acidmentioning

confidence: 99%

The role of retinoic acid in embryonic and post-embryonic development

Maden

2000

Proc. Nutr. Soc.

116

View full text Add to dashboard Cite

show abstract

“…It was assumed that digit formation is induced by a concentration gradient (high posteriorly) of all-trans-RA along the anterior-posterior axis; all-trans-RA is synthesised through the sequential oxidation of retinol and retinaldehyde [31]. The gradient of alltrans-RA is strengthened by a reverse gradient (high anteriorly) of cytosolic retinoic acid binding protein (CRABP), which is supposed to lower the concentration of free all-trans-RA available for binding to the nuclear receptor [14,28,29]. In addition, 3,4-didehydroretinoic acid (ddRA) and its precursor 3,4-didehydroretinol (ddROH) were identified and quantified in chick limb buds [28,32].…”

Section: Introductionmentioning

confidence: 99%

“…The gradient of alltrans-RA is strengthened by a reverse gradient (high anteriorly) of cytosolic retinoic acid binding protein (CRABP), which is supposed to lower the concentration of free all-trans-RA available for binding to the nuclear receptor [14,28,29]. In addition, 3,4-didehydroretinoic acid (ddRA) and its precursor 3,4-didehydroretinol (ddROH) were identified and quantified in chick limb buds [28,32]. However, numerous differences between chicks and mice exist with respect to the endogenous retinoid profile in embryonic limb buds.…”

Section: Introductionmentioning

confidence: 99%

“…However, numerous differences between chicks and mice exist with respect to the endogenous retinoid profile in embryonic limb buds. Although all-trans-RA and retinol (ROH) were also found in the limb buds of mouse embryos, neither a posterior nor anterior gradient of the concentrations of these retinoids was found, nor were ddRA, ddROH or retinyl esters detected in the mouse limb buds [25,28], indicating possible differences between mammals and birds.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Distribution of endogenous retinoids, retinoid binding proteins (RBP, CRABPI) and nuclear retinoid X receptor ? (RXR?) in the porcine embryo

et al. 2002

Self Cite

View full text Add to dashboard Cite

-Retinoids are important signalling molecules in the development of limbs and in the determination of the anterior-posterior orientation of the embryo. The present study examined the content and distribution of retinoic acid, retinol and retinyl esters in porcine embryos during early gestation (gestation days 22-30) macroscopically and microscopically by its autofluorescence and by HPLC. Macroscopically, the yellowish-greenish autofluorescence characteristic of vitamin A was observed in tissues affected by morphogenesis, such as the limbs, in a spatial and temporal manner. Changes in the intensity of autofluorescence in the limbs paralleled changes in the concentration of retinoids in these structures. In the limbs and the body, retinol, retinyl palmitate, and all-trans-retinoic acid but neither the isomers of all-trans retinoic acid nor other retinoid metabolites were detected. In addition, the distribution of specific retinoid-binding proteins was investigated; these are involved in vitamin A transport, metabolism and signal transduction. Immunoreactive retinol-binding protein as well as cellular retinoic acid binding protein type I were only localised in the mesonephros, while the retinoid X receptor b was widely distributed in most of the tissues and organs of the embryo throughout the time period investigated. The combination of autofluorescence and HPLC analysis allowed for the first time to attribute the yellowish-greenish autofluorescence in specific regions of the embryo to vitamin A, and offers a method to study the local cellular distribution of retinol and/or retinyl esters as well as their concentrations in embryonic tissues. retinoid / vitamin A / binding protein / nuclear receptor / autofluorescence / embryo / pig Reprod. Nutr. Dev. 42 (2002) 285-294 285

show abstract

“…This suggests that Shh activation by RA may be indirect. Endogenous RA was originally reported to be higher posteriorly in limb buds, supporting a role for RA in imparting anteroposterior information (13), but measurements by others have disputed this conclusion (14,15). Also, the ZPA has been demonstrated to be devoid of local RA synthesis, indicating that the posterior region of limb buds does not generate RA (16,17).…”

mentioning

confidence: 99%

Retinoic Acid Synthesis Controlled by Raldh2 Is Required Early for Limb Bud Initiation and Then Later as a Proximodistal Signal during Apical Ectodermal Ridge Formation

Mic

Sîrbu

Duester

2004

Journal of Biological Chemistry

103

View full text Add to dashboard Cite

We present evidence for the existence of two phases of retinoic acid (RA) signaling required for vertebrate limb development. Limb RA synthesis is under the control of retinaldehyde dehydrogenase-2 (Raldh2) expressed in the lateral plate mesoderm, which generates a proximodistal RA signal during limb outgrowth. We report that Raldh2 ؊/؊ embryos lack trunk mesodermal RA activity and fail to initiate forelimb development. This is associated with deficient expression of important limb determinants Tbx5, Meis2, and dHand needed to establish forelimb bud initiation, proximal identity, and the zone of polarizing activity (ZPA), respectively. Limb expression of these genes can be rescued by maternal RA treatment limited to embryonic day 8 (E8) during limb field establishment, but the mutant forelimbs obtained at E10 display a significant growth defect associated with a smaller apical ectodermal ridge (AER), referred to here as an apical ectodermal mound (AEM). In these RA-deficient forelimbs, a ZPA expressing Shh forms, but it is located distally adjacent to the Fgf8 expression domain in the AEM rather than posteriorly as is normal. AER formation in Raldh2 ؊/؊ forelimbs is rescued by continuous RA treatment through E10, which restores RA to distal ectoderm fated to become the AER. Our findings indicate the existence of an early phase of RA signaling acting upstream of Tbx5, Meis2, and dHand, followed by a late phase of RA signaling needed to expand AER structure fully along the distal ectoderm. During ZPA formation, RA acts early to activate expression of dHand, but it is not required later for Shh activation.

show abstract

Endogenous Status of Retinoids and Their Cytosolic Binding Proteins in Limb Buds of Chick vs Mouse Embryos

Cited by 60 publications

References 0 publications

The role of retinoic acid in embryonic and post-embryonic development

The role of retinoic acid in embryonic and post-embryonic development

Distribution of endogenous retinoids, retinoid binding proteins (RBP, CRABPI) and nuclear retinoid X receptor ? (RXR?) in the porcine embryo

Retinoic Acid Synthesis Controlled by Raldh2 Is Required Early for Limb Bud Initiation and Then Later as a Proximodistal Signal during Apical Ectodermal Ridge Formation

Contact Info

Product

Resources

About