All-trans retinoic acid (RA) is a key player in many developmental pathways. Most methods used to study its effects in development involve continuous all-trans RA activation by incubation in a solution of all-trans RA or by implanting all-trans RA-soaked beads at desired locations in the embryo. Here we show that the UV-driven photo-isomerization of 13-cis RA to the trans-isomer (and vice versa) can be used to non-invasively and quantitatively control the concentration of all-trans RA in a developing embryo in time and space. This facilitates the global or local perturbation of developmental pathways with a pulse of all-trans RA of known concentration or its inactivation by UV illumination. In zebrafish embryos in which endogenous synthesis of all-trans RA is impaired, incubation for as little as 5 minutes in 1 nM all-trans RA (a pulse) or 5 nM 13-cis RA followed by 1-minute UV illumination is sufficient to rescue the development of the hindbrain if performed no later than bud stage. However, if subsequent to this all-trans RA pulse the embryo is illuminated (no later than bud stage) for 1 minute with UV light (to isomerize, i.e. deactivate, all-trans RA), the rescue of hindbrain development is impaired. This suggests that all-trans RA is sequestered in embryos that have been transiently exposed to it. Using 13-cis RA isomerization with UV light, we further show that local illumination at bud stage of the head region (but not the tail) is sufficient to rescue hindbrain formation in embryos whose all-trans RA synthetic pathway has been impaired.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1242/dev.077776 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Zebrafish modeling of atypical PML-RARA isoform from acute promyelocytic leukemia patient and its implications for clinical treatment.
Ann Hematol
January 2025
Department of Hematology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, China.
Acute promyelocytic leukemia (APL) is driven by the specific fusion gene PML-RARA produced by chromosomal translocation. Three classic isoforms, L, V, and S, are found in more than 95% of APL patients. However, atypical PML-RARA isoforms are usually associated with uncertain disease progression and treatment prognosis.
View Article and Find Full Text PDFStudy protocol: multi-centre, randomised controlled clinical trial exploring stromal targeting in locally advanced pancreatic cancer; STARPAC2.
BMC Cancer
January 2025
Barts Cancer Institute and Wolfson Institute of Public Health, Mary University of London, John Vane Science Centre, Charterhouse Square, London, Queen, EC1M 6BQ, UK.
Background: Pancreatic cancer (PDAC: pancreatic ductal adenocarcinoma, the commonest form), a lethal disease, is best treated with surgical excision but is feasible in less than a fifth of patients. Around a third of patients presentlocally advanced, inoperable, non-metastatic (laPDAC), whose stadrd of care is palliative chemotherapy; a small minority are down-sized sufficiently to enable surgical excision. We propose a phase II clinical trial to test whether a combination of standard chemotherapy (gemcitabine & nab-Paclitaxel: GEM-NABP) and repurposing All Trans Retinoic Acid (ATRA) to target the stroma may extend progression-free survival and enable successful surgical resection for patients with laPDAC, since data from phase IB clinical trial demonstrate safety of GEM-NABP-ATRA combination to patients with advanced PDAC with potential therapeutic benefit.
View Article and Find Full Text PDFInfluence of macrophages and neutrophilic granulocyte-like cells on crystalline silica-induced toxicity in human lung epithelial cells.
Toxicol Res (Camb)
February 2025
Département Toxicologie et Biométrologie, Institut National de Recherche et de Sécurité pour la prévention des accidents du travail et des maladies professionnelles (INRS), 1 rue du Morvan, 54519 Vandœuvre-lès-Nancy, France.
In many industrial activities, workers may be exposed by inhalation to particles that are aerosolized, To predict the human health hazard of these materials, we propose to develop a co-culture model (macrophages, granulocytes, and alveolar epithelial cells) designed to be more representative of the inflammatory pulmonary response occurring in vivo. Phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 cells were used as macrophages, All-trans retinoic acid (ATRA)-differentiated HL60 were used as granulocytes and A549 were used as epithelial alveolar type II cells. A crystalline silica sample DQ12 was used as a prototypical particle for its capabilities to induce DNA damage, inflammatory response, and oxidative stress in epithelial cells; its polyvinylpyridine-N-oxide (PVNO)-surface modified counterpart was also used as a negative particulate control.
View Article and Find Full Text PDFBioorthogonal chemical reporters for profiling retinoic acid-modified and retinoic acid-interacting proteins.
Bioorg Med Chem
January 2025
State Key Laboratory of Chemical Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, China. Electronic address:
Vitamin A and its primary active derivative, all-trans retinoic acid (RA), are endogenous signaling molecules essential for numerous biological processes, including cell proliferation, differentiation, and immune modulation. Owing to its differentiation-inducing effect, RA was the first differentiating agent approved for the clinical treatment of acute myeloid leukemia. While the classical mechanisms of RA signaling involve nuclear receptors, such as retinoic acid receptors (RARs), emerging evidence suggests that RA also engages in non-covalent and covalent interactions with a broader range of proteins.
View Article and Find Full Text PDFQuantitative Analysis of Dietary Vitamin A Metabolites in Murine Ocular and Non-Ocular Tissues Using High-Performance Liquid Chromatography.
J Vis Exp
December 2024
Department of Ophthalmology and Visual Neurosciences, University of Minnesota;
G protein-coupled receptors (GPCRs) are a superfamily of transmembrane proteins that initiate signaling cascades through activation of its G protein upon association with its ligand. In all mammalian vision, rhodopsin is the GPCR responsible for the initiation of the phototransduction cascade. Within photoreceptors, rhodopsin is bound to its chromophore 11-cis-retinal and is activated through the light-sensitive isomerization of 11-cis-retinal to all-trans-retinal, which activates the transducin G protein, resulting in the phototransduction cascade.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!