Journal ArticleDOI
Endogenous distribution of retinoids during normal development and teratogenesis in the mouse embryo
Claire Horton,Malcolm Maden +1 more
TLDR
It is concluded that other factors, for example, nuclear factors, must be responsible for the teratogenic response to RA and not cell‐specific factors, as previously concluded.Abstract:
We have analysed the endogenous retinoids present in whole mouse embryos from day 9 to day 14 of development and in individual components of the embryo at two stages, day 10.5 and day 13, by HPLC. We can only detect two retinoids, all-trans-RA (tRA) and all-trans-retinol (t-retinol), and t-retinol is 5-10-fold in excess over tRA. We cannot detect 9-cis-RA or any didehydroretinoids; thus mammalian embryos seem to differ in their retinoid content from other embryos such as chick, Xenopus, and fish. The levels of tRA do not change significantly over the 6 days of development analysed, whereas t-retinol rises sharply as the liver develops. Within the embryo, tRA is present at high levels in the developing spinal cord and at very low levels in the forebrain; indeed there is a gradient of endogenous tRA from the forebrain to the spinal cord. Other parts of the embryo had intermediate levels of tRA. When a teratogenic dose of RA was administered to day 10.5 embryos, the levels of tRA present in individual tissues of the embryo rose dramatically--from 175-fold to 1,400-fold--and the levels rose in all tissues not in any exclusive areas. We then determined which areas of the embryo were malformed by such a teratogenic dose. The lower jaw, palate, vertebrae, tail, and limbs were consistently abnormal, and since these areas received a dose of tRA no higher than any other it was concluded that cell-specific factors must determine the teratogenic response of these tissues. We then considered whether cellular retinoic acid-binding protein I or II (CRABP I or II) played any role in this response by determining their relative levels in each of the tissues analysed. There was no correlation between the presence of CRABP I and II and the distribution of administered RA. Neither was there a clear correlation in detail between the presence of CRABP I and II and the sites of teratogenesis. We therefore conclude that other factors, for example, nuclear factors, must be responsible for the teratogenic response to RA.read more
Citations
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Journal ArticleDOI
Retinoids in Embryonal Development
Sharon A. Ross,Sharon A. Ross,Sharon A. Ross,Peter McCaffery,Peter McCaffery,Peter McCaffery,Ursula C. Dräger,Ursula C. Dräger,Ursula C. Dräger,Luigi M. De Luca,Luigi M. De Luca,Luigi M. De Luca +11 more
TL;DR: The key role of vitamin A in embryonal development is reviewed and special emphasis is given to the physiological action of retinoids, as evident from the retinoid ligand knockout models.
Journal ArticleDOI
Docosahexaenoic Acid, a Ligand for the Retinoid X Receptor in Mouse Brain
Alexander Mata de Urquiza,Suya Liu,Maria Sjöberg,Rolf Zetterström,William J. Griffiths,Jan Sjövall,Thomas Perlmann +6 more
TL;DR: DHA, a long-chain polyunsaturated fatty acid that is highly enriched in the adult mammalian brain, is identified as a factor in brain tissue from adult mice that activates RXR in cell-based assays, suggesting that DHA may influence neural function through activation of an RXR signaling pathway.
Journal ArticleDOI
Diversity and Pattern in the Developing Spinal Cord
Yasuto Tanabe,Thomas M. Jessell +1 more
TL;DR: This work uses the spinal cord as a model system for analyzing the molecular control of central nervous system development in vertebrates and reveals the identity and mechanism of action of molecules that induce and pattern neural tissue and the role of transcription factors in establishing generic and specific neuronal fates.
Journal ArticleDOI
FUNCTION OF RETINOID NUCLEAR RECEPTORS: Lessons from Genetic and Pharmacological Dissections of the Retinoic Acid Signaling Pathway During Mouse Embryogenesis
TL;DR: Genetic and pharmacological studies in the mouse demonstrate that RXR/RAR heterodimers in which RXR is either transcriptionally active or silent are involved in the transduction of the RA signal during prenatal development, and the physiological role of RA and its receptors cannot be extrapolated from teratogenesis studies using retinoids in excess.
Journal ArticleDOI
ErbB3 is required for normal cerebellar and cardiac development: a comparison with ErbB2-and heregulin-deficient mice
TL;DR: The cranial ganglia defects, along with a dramatic reduction in Schwann cells, enteric ganglia and adrenal chromaffin cells, suggests a generalized effect on the neural crest and Numerous organs, including the stomach and pancreas also exhibited anomalous development.
References
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Journal ArticleDOI
Homeotic transformations of murine vertebrae and concomitant alteration of Hox codes induced by retinoic acid
Michael Kessel,Peter Gruss +1 more
TL;DR: It is suggested that the identity of a vertebral segment is specified by a combination of functionally active Hox genes, a "Hox code," and that exogenous RA interferes with the normal establishment of Hox codes and thus with axial specification.
Journal ArticleDOI
Function of the retinoic acid receptors (RARs) during development (II). Multiple abnormalities at various stages of organogenesis in RAR double mutants
Cathy Mendelsohn,David Lohnes,Didier Decimo,Thomas Lufkin,Marianne LeMeur,Pierre Chambon,Manuel Mark +6 more
TL;DR: The results clearly demonstrate that RARs are essential for vertebrate ontogenesis and therefore that retinoic acid is the active retinoid, which is required at several stages of the development of numerous tissues and organs.
Journal ArticleDOI
Identification and spatial distribution of retinoids in the developing chick limb bud.
Christina Thaller,Gregor Eichele +1 more
TL;DR: It is reported that chick limb buds contain endogenous RA and it is shown that RA, but not its biosynthetic precursor retinol, forms a concentration gradient across the limb anlage with a high-point in the posterior domain of the limb bud, the part that also contains the ZPA.
Journal ArticleDOI
Retinoic acid causes an anteroposterior transformation in the developing central nervous system.
Antony J. Durston,J. P. M. Timmermans,W. J. Hage,H.F.J. Hendriks,N. J. de Vries,M. Heideveld,P. D. Nieuwkoop +6 more
TL;DR: It is found that RA acts on the developing CNS, transforming anterior neural tissue to a posterior neural specification, raising the possibility that RA mediates an inductive interaction regulating anteroposterior differentiation within the CNS.
Journal ArticleDOI
Function of the retinoic acid receptors (RARs) during development (I). Craniofacial and skeletal abnormalities in RAR double mutants
David Lohnes,Manuel Mark,Cathy Mendelsohn,Pascal Dollé,Andrée Dierich,Philippe Gorry,Anne Gansmuller,Pierre Chambon +7 more
TL;DR: Multiple eye abnormalities are described which are found in various RAR double mutant fetuses and are similar to those previously seen in VAD fetuses, and further abnormalities not previously reported in Vad fetuses are found.