The retinoic acid-metabolizing enzyme, CYP26A1, is essential for normal hindbrain patterning, vertebral identity, and development of posterior structures
Suzan Abu-Abed,Pascal Dollé,Daniel Metzger,Barbara R. Beckett,Pierre Chambon,Martin Petkovich +5 more
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It is postulate that the key function of CYP26A1 is to maintain specific embryonic areas in a RA-depleted state, to protect them against the deleterious effect of ectopic RA signaling.Abstract:
The active derivative of vitamin A, retinoic acid (RA), is essential for normal embryonic development. The spatio-temporal distribution of embryonic RA results from regulated expression of RA-synthesizing retinaldehyde dehydrogenases and RA-metabolizing cytochrome P450s (CYP26). Excess RA administration or RA deficiency results in a complex spectrum of embryonic abnormalities. As a first step in understanding the developmental function of RA-metabolizing enzymes, we have disrupted the murine Cyp26A1 gene. We report that Cyp26A1-null mutants die during mid-late gestation and show a number of major morphogenetic defects. Spina bifida and truncation of the tail and lumbosacral region (including abnormalities of the kidneys, urogenital tract, and hindgut) are the most conspicuous defects, leading in extreme cases to a sirenomelia (“mermaid tail”) phenotype. Cyp26A1 mutants also show posterior transformations of cervical vertebrae and abnormal patterning of the rostral hindbrain, which appears to be partially posteriorly transformed. These defects correlate with two major sites of Cyp26A1 expression in the rostral neural plate and embryonic tail bud. Because all of the Cyp26A1−/− abnormalities closely resemble RA teratogenic effects, we postulate that the key function of CYP26A1 is to maintain specific embryonic areas in a RA-depleted state, to protect them against the deleterious effect of ectopic RA signaling.read more
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Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis
Minoru Takasato,Minoru Takasato,Pei Xuan Er,Han Sheng Chiu,Barbara Maier,Gregory J. Baillie,Charles Ferguson,Robert G. Parton,Ernst J. Wolvetang,Matthias S Roost,Susana M. Chuva de Sousa Lopes,Melissa H. Little,Melissa H. Little,Melissa H. Little +13 more
TL;DR: The developmental mechanism regulating the preferential induction of collecting duct versus kidney mesenchyme progenitors is identified and kidney organoids that contain nephrons associated with a collecting duct network surrounded by renal interstitium and endothelial cells are generated.
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Retinoic acid regulates sex-specific timing of meiotic initiation in mice.
TL;DR: In this paper, the authors examined the mechanism underlying the sex-specific timing of Stra8 expression and meiotic initiation in mice and showed that signaling by retinoic acid (RA), an active derivative of vitamin A, is required for Stra8expression and thereby meiosis initiation in embryonic ovaries.
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Retinoic acid signalling during development
Muriel Rhinn,Pascal Dollé +1 more
TL;DR: An overview of the RA biosynthesis, degradation and signalling pathways is provided and the main functions of this molecule during embryogenesis are reviewed.
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Retinoic acid in development: towards an integrated view
Karen Niederreither,Pascal Dollé +1 more
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References
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Journal ArticleDOI
A decade of molecular biology of retinoic acid receptors.
TL;DR: A review of recent developments in structure‐ function relationships of retinoic acid receptors focuses on recent developments, particularly in the area of structure‐function relationships.
Book
The Retinoids : biology, chemistry, and medicine
TL;DR: Retinoids In Photosensitive Systems John C. Saari Introduction / Overview of the Visual Process / Chromophores of Visual Pigments /photoisomerisation / Wavelength Regulation The Visual Cycle /Cellular Uptake of Retinol.
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Embryonic retinoic acid synthesis is essential for early mouse post-implantation development.
TL;DR: It is established that RA synthesized by the post-implantation mammalian embryo is an essential developmental hormone whose lack leads to early embryo death.
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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.