Background: The X-chromosomally linked gene WTX is a human disease gene and a member of the AMER family. Mutations in WTX are found in Wilms tumor, a form of pediatric kidney cancer and in patients suffering from OSCS (Osteopathia striata with cranial sclerosis), a sclerosing bone disorder. Functional data suggest WTX to be an inhibitor of the Wnt/β-catenin signaling pathway. Deletion of Wtx in mouse leads to perinatal death, impeding the analysis of its physiological role.
Results: To gain insights into the function of Wtx in development and homeostasis we have used zebrafish as a model and performed both knockdown and knockout studies using morpholinos and transcription activator-like effector nucleases (TALENs), respectively. Wtx knockdown led to increased Wnt activity and embryonic dorsalization. Also, wtx mutants showed a transient upregulation of Wnt target genes in the context of caudal fin regeneration. Surprisingly, however, wtx as well as wtx/amer2/amer3 triple mutants developed normally, were fertile and did not show any anomalies in organ maintenance.
Conclusions: Our data show that members of the zebrafish wtx/amer gene family, while sharing a partially overlapping expression pattern do not compensate for each other. This observation demonstrates a remarkable robustness during development and regeneration in zebrafish.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/dvdy.84 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Accelerated MR cell size imaging through parallel acquisition technique (PAT) and simultaneous multi-slice (SMS) with local principal component analysis (LPCA) enhancement.
Magn Reson Imaging
January 2025
Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital of Sichuan University, No.37 Guo Xue Alley, Chengdu, Sichuan 610041, China. Electronic address:
Microstructural parameters are essential in tumor research, aiding in the understanding tumor pathogenesis, grading, and therapeutic efficacy. The imaging microstructural parameters using limited spectrally edited diffusion (IMPULSED) model is the most widely used MR cell size imaging technique, demonstrating success in measuring microstructural parameters of solid tumors in vivo. However, its clinical application is limited by the longer scan times required for both pulsed gradient spin-echo (PGSE) and multiple oscillating gradient spin-echo (OGSE) acquisitions across a range of b-values, which can be burdensome for patients and disrupt clinical workflows.
View Article and Find Full Text PDFNon-conventional toxin WTX and its disulfide-fixed synthetic fragments: Interaction with nicotinic acetylcholine receptors and reduction of blood pressure.
Int J Biol Macromol
February 2025
Department of Molecular Neuroimmune Signaling, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10 Miklukho-Maklay Str., 117997 Moscow, Russia. Electronic address:
Non-conventional snake venom toxins, such as WTX from the cobra Naja kaouthia, are three-finger proteins containing a fifth disulfide bond in the N-terminal polypeptide loop I and inhibiting α7 and muscle-type nicotinic acetylcholine receptors (nAChRs). Because the central polypeptide loop II of non-conventional toxins plays an important role in their biological activity, we synthesized several WTX loop II fragments with two cysteine residues added at the N- and C-termini and oxidized to form a disulfide bond. The inhibition by peptides of several nAChRs subtypes was investigated using different methods and the effects of peptides on the rat arterial pressure and heart rate were analyzed.
View Article and Find Full Text PDFMulti-platform analysis revealed the substance basis and mechanism of Wei-Tong-Xin in ameliorating ENS dysfunction for dyspepsia treatment.
J Ethnopharmacol
January 2025
Faculty of Functional Food and Wine, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, 110016, China. Electronic address:
Article Synopsis
- Duodenal motility disorder plays a role in causing dyspepsia, and the traditional Chinese medicine formula Wei-Tong-Xin (WTX) has shown effectiveness in relieving this condition.
- The study aims to analyze the chemical composition of WTX and understand how it works to alleviate dyspepsia through a comprehensive approach including advanced analytical techniques and network pharmacology.
- The research identified 100 chemical components in WTX, revealing that its therapeutic effects may involve regulating inflammation and oxidative stress, ultimately improving intestinal health and function in a mouse model of dyspepsia.
Homocysteine-potentiated Kelch-like ECH-associated protein 1 promotes senescence of neuroblastoma 2a cells via inhibiting ubiquitination of β-catenin.
Eur J Neurosci
May 2024
Department of Pathophysiology, School of Basic Medicine, Key Laboratory of Education Ministry of China/Hubei Province for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Elevated serum homocysteine (Hcy) level is a risk factor for Alzheimer's disease (AD) and accelerates cell aging. However, the mechanism by which Hcy induces neuronal senescence remains largely unknown. In this study, we observed that Hcy significantly promoted senescence in neuroblastoma 2a (N2a) cells with elevated β-catenin and Kelch-like ECH-associated protein 1 (KEAP1) levels.
View Article and Find Full Text PDFErratum to: Synthetic Peptide Fragments of the Wtx Toxin Reduce Blood Pressure in Rats under General Anesthesia.
Dokl Biochem Biophys
December 2023
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
Want 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!