AI Article Synopsis
- The study investigates the role of DNA methyltransferase 1 (DNMT1) in the development of the auditory system using zebrafish as a model organism.
- Researchers induced Dnmt1 deficiency using morpholino oligonucleotides and analyzed the effects through various methods like RNA sequencing and immunostaining.
- Findings showed that downregulating Dnmt1 led to reduced neuromasts, inhibited cell growth, malformed otoliths, and disruption in hair cell differentiation, emphasizing DNMT1's crucial role in auditory organ development by regulating cell cycle and critical signaling pathways.
Article Abstract
Objectives: To explore the role of DNA methyltransferase 1 (DNMT1) in the development of auditory system using zebrafish as experimental model.
Methods: Morpholino oligonucleotide was used to induce Dnmt1 deficiency. RNA sequencing, in situ hybridization (ISH), whole genomic bisulfide sequencing (WGBS) and immunostaining were used to investigate the morphologic alterations and mechanisms.
Results: We found that downregulation of Dnmt1 induced decreased number of neuromasts and repressed cell proliferation of primordium in the developing posterior lateral line system of zebrafish. The ISH data uncovered that Fgf signalling pathway was inhibited and the expression of chemokine members cxcr4b, cxcr7b and cxcl12a were interfered, while lef1 expression was increased after inhibiting Dnmt1. Additionally, Dnmt1 downregulation led to malformed otoliths and deformed semicircular canals, and hair cell differentiation in utricle and saccule was inhibited severely. The in situ staining of otic placode markers pax2/5 and fgf 3/8/10 was decreased when Dnmt1 downregulated. The WGBS analysis demonstrated that the global methylation status was markedly downregulated, and cell cycle genes were among those most differently expressed between Dnmt1 morphants and the controls. Further ISH analysis confirmed the findings by RNA-seq and WGBS assay that cdkn1a and tp53 were both upregulated after knockdown of Dnmt1.
Conclusion: Our results revealed that Dnmt1 is essential for the development of zebrafish auditory organ through regulating cell cycle genes together with Wnt and Fgf signalling pathways.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9136517 | PMC |
| http://dx.doi.org/10.1111/cpr.13225 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Exploring 1,2,3-triazole-Schiff's base hybrids as innovative EGFR inhibitors for the treatment of breast cancer: In vitro and in silico study.
Bioorg Chem
January 2025
Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt. Electronic address:
EGFR inhibitors are a class of targeted therapies utilized in the management of certain tumor kinds such as NSCLC and breast cancer. Series of 1,2,3-triazole-Schiff's base hybrids were designed, synthesized, and estimated for their antitumor effect toward breast cancer cells, MCF-7 and MDA-MB-231. The safety and selectivity of the new compounds were tested using normal cell (WI-38).
View Article and Find Full Text PDFElevated plasma molybdenum level increases the risk of premature ovarian insufficiency through vascular endothelial injury.
Hum Reprod
January 2025
The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Study Question: Is elevated plasma molybdenum level associated with increased risk for idiopathic premature ovarian insufficiency (POI)?
Summary Answer: Elevated plasma molybdenum level is associated with an increased risk of idiopathic POI through vascular endothelial injury and inhibition of granulosa cell proliferation.
What Is Known Already: Excessive molybdenum exposure has been associated with ovarian oxidative stress in animals but its role in the development of POI remains unknown.
Study Design, Size, Duration: Case-control study of 30 women with idiopathic POI and 31 controls enrolled from August 2018 to May 2019.
Distinct and interdependent functions of three RING proteins regulate recombination during mammalian meiosis.
Proc Natl Acad Sci U S A
January 2025
HHMI, University of California, Davis, CA 95616.
During meiosis, each pair of homologous chromosomes becomes connected by at least one crossover, as required for accurate segregation, and adjacent crossovers are widely separated thereby limiting total numbers. In coarsening models, this crossover patterning results from nascent recombination sites competing to accrue a limiting pro-crossover RING-domain protein (COR) that diffuses between synapsed chromosomes. Here, we delineate the localization dynamics of three mammalian CORs in the mouse and determine their interdependencies.
View Article and Find Full Text PDFChronotherapy with Cinacalcet has a striking effect on inhibition of parathyroid gland proliferation in rats with secondary hyperparathyroidism.
PLoS One
January 2025
Nephrological Department, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark.
Secondary hyperparathyroidism (sHPT) is a significant clinical complication of CKD leading to bone abnormalities and cardiovascular disease. Current treatment based on activating the parathyroid calcium-sensing receptor (CaSR) using calcimimetics such as Cinacalcet, aims to decrease plasma PTH levels and inhibit the progression of parathyroid hyperplasia. In the present study, we found significant diurnal rhythmicity of Casr, encoding the Cinacalcet drug target in hyperplastic parathyroid glands (p = 0.
View Article and Find Full Text PDFFAK inhibition delays liver repair after acetaminophen-induced acute liver injury by suppressing hepatocyte proliferation and macrophage recruitment.
Hepatol Commun
November 2024
Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, China.
Background: Overdose of acetaminophen (APAP), a commonly used antipyretic analgesic, can lead to severe liver injury and failure. Current treatments are only effective in the early stages of APAP-induced acute liver injury (ALI). Therefore, a detailed examination of the mechanisms involved in liver repair following APAP-induced ALI could provide valuable insights for clinical interventions.
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!