To study retinoid signaling in the developing telencephalon, we transfected a retinoid reporter gene into different regions of developing telencephalon. We found that the ventral telencephalon was more competent to retinoid signaling than the dorsal telencephalon. Moreover, among all retinoic acid receptors (RARs) and retinoid X receptors (RXRs), RARbeta was strongly induced by retinoic acid in the ventral telencephalon, suggesting that RARbeta might be involved in retinoid signaling competence. The RT-PCR analysis indicated that RARbeta was selectively expressed in the developing striatum of ventral telencephalon. We then demonstrated that null mutations of RARbeta gene resulted in reduction of striatal-enriched tyrosine phosphatase (STEP) mRNA in the striatum of RARbeta-/- mutant mice. Conversely, the gain-of-function study showed that ectopic expression of RARbeta1 in the cerebral cortex enhanced STEP expression, and the effect was RARbeta-isoform specific. Our study identified RARbeta as an important molecule for transducing retinoid signals in developing ventral telencephalon.
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http://dx.doi.org/10.1002/dvdy.20281 | DOI Listing |
Proc Natl Acad Sci U S A
February 2025
Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.
Classical tissue recombination experiments demonstrate that cell-fate determination along the anterior-posterior axis of the Müllerian duct occurs prior to postnatal day 7 in mice. However, little is known about how these cell types are maintained in adults. In this study, we provide genetic evidence that a balance between antagonistic retinoic acid (RA) and estrogen signaling activity is required to maintain simple columnar cell fate in adult uterine epithelium.
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January 2025
Department of Pharmacology and Cleveland Center for Membrane and Structural Biology, Case Western Reserve University, Cleveland, OH, United States.
Alterations in tissue expression levels of both retinol-binding protein 2 (RBP2) and retinol-binding protein 4 (RBP4) have been associated with metabolic disease, specifically with obesity, glucose intolerance and hepatic steatosis. Our laboratories have shown that this involves novel pathways not previously considered as possible linkages between impaired retinoid metabolism and metabolic disease development. We have established both biochemically and structurally that RBP2 binds with very high affinity to very long-chain unsaturated 2-monoacylglycerols like the canonical endocannabinoid 2-arachidonoyl glycerol (2-AG) and other endocannabinoid-like substances.
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January 2025
Université de Strasbourg, IGBMC UMR 7104, Illkirch, France; CNRS, UMR 7104, Illkirch, France; Inserm, UMR-S 1258, Illkirch, France; IGBMC, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France. Electronic address:
In mammals, differentiation of germ cells is crucial for sexual reproduction, involving complex signaling pathways and environmental cues defined by the somatic cells of the gonads. This review examines the long-standing model positing that all-trans retinoic acid (ATRA) acts as a meiosis-inducing substance (MIS) in the fetal ovary by inducing expression of STRA8 in female germ cells, while CYP26B1 serves as a meiosis-preventing substance (MPS) in the fetal testis by degrading ATRA and preventing STRA8 expression in the male germ cells until postnatal development. Recent genetic studies in the mouse challenge this paradigm, revealing that meiosis initiation in female germ cells can occur independently of ATRA signaling, with key roles played by other intrinsic factors like DAZL and DMRT1, and extrinsic signals such as BMPs and vitamin C.
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January 2025
Department of Oral Immunology and Infectious Diseases, University of Louisville School of Dentistry, Louisville, KY, United States. Electronic address:
Retinoic acid (RA) signaling plays multiple essential roles in development of the head and face. Animal models with mutations in genes involved in RA signaling have enabled understanding of craniofacial morphogenic processes that are regulated by the retinoid pathway. During craniofacial morphogenesis RA signaling is active in spatially restricted domains defined by the expression of genes involved in RA production and RA breakdown.
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January 2025
Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, OH, United States. Electronic address:
Animals perceiving light through visual pigments have evolved pathways for absorbing, transporting, and metabolizing the precursors essential for synthesis of their retinylidene chromophores. Over the past decades, our understanding of this metabolism has grown significantly. Through genetic manipulation, researchers gained insights into the metabolic complexity of the pathways mediating the flow of chromophore precursors throughout the body, and their enrichment within the eyes.
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