Aims: Notch signalling is essential for blood vessel formation. During angiogenesis, the Notch ligand DLL4 on the leading tip cell activates Notch receptors on the adjacent stalk cells. DLL4-Notch signalling is impaired by the Notch ligand JAG1 in endothelial cells. The Delta/Serrate/Lag2 (DSL) domain of the Notch ligands binds to the EGF-like repeats 11-13 of the Notch receptor. This study aimed to elucidate how soluble proteins containing these short domains interfere with Notch signalling during angiogenesis.
Methods And Results: Adenoviral vectors were generated to express the DSL domains of DLL1, DLL4, JAG1, and the Notch1 EGF-like repeats 11-13 fused to immunoglobulin-G heavy chain. These soluble ligand peptides inhibited Notch signalling in endothelial cells and this caused hyperbranching in cellular angiogenesis assays and in the neonatal mouse retina. The soluble Notch receptor peptides bound stronger to JAG1 than DLL4 ligands, resulting in increased signalling activity. This led to impaired tip cell formation and less vessel sprouting in the retina.
Conclusion: The minimal binding domains of Notch ligands are sufficient to interfere with Notch signalling. The corresponding soluble Notch1 EGF11-13 peptide binds stronger to inhibitory Notch ligands and thereby promotes Notch signalling in endothelial cells.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1093/cvr/cvv151 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Piezo1 aggravates ischemia/reperfusion-induced acute kidney injury by Ca-dependent calpain/HIF-1α/Notch signaling.
Ren Fail
December 2025
Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, China.
Macrophages play a vital role in the inflammation and repair processes of ischemia/reperfusion-induced acute kidney injury (IR-AKI). The mechanosensitive ion channel Piezo1 is significant in these inflammatory processes. However, the exact role of macrophage in IR-AKI is unknown.
View Article and Find Full Text PDFis required to maintain supporting cell identity and vestibular function during maturation of the mammalian balance organs.
J Neurosci
January 2025
Flaum Eye Institute, Department of Ophthalmology, University of Rochester Medical Center, Rochester, New York, 14642, USA;
The inner ear houses both hearing and balance sensory modalities. The hearing and balance organs consist of similar cell types, including sensory hair cells and associated supporting cells. Previously we showed that is required for maintaining supporting cell survival during cochlear maturation.
View Article and Find Full Text PDFPosttranscriptional Control of Neural Progenitors Temporal Dynamics During Neocortical Development by Syncrip.
Adv Sci (Weinh)
January 2025
State Key Laboratory of Common Mechanism Research for Major Diseases, Department of Biochemistry & Molecular Biology, Medical Primate Research Center, Neuroscience Center, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, China.
The development of the mammalian neocortex is precisely regulated by temporal gene expression, yet the temporal regulatory mechanisms of cortical neurogenesis, particularly how radial glial cells (RGCs) sequentially generate deep to superficial neurons, remain unclear. Here, the hnRNP family member Syncrip (hnRNP Q) is identified as a key modulator of superficial neuronal differentiation in neocortical neurogenesis. Syncrip knockout in RGCs disrupts differentiation and abnormal neuronal localization, ultimately resulting in superficial cortical layer defects as well as learning and memory impairments in mice.
View Article and Find Full Text PDFA Novel Glycoengineered Humanized Antibody Targeting DLK1 Exhibits Potent Anti-Tumor Activity in DLK1-Expressing Liver Cancer Cell Xenograft Models.
Int J Mol Sci
December 2024
Chiome Bioscience Inc., 3-12-1 Honmachi, Shibuya-ku, Tokyo 151-0071, Japan.
Delta-like 1 homolog (DLK1), a non-canonical Notch ligand, is highly expressed in various malignant tumors, especially in hepatocellular carcinoma (HCC). CBA-1205 is an afucosylated humanized antibody against DLK1 with enhanced antibody-dependent cellular cytotoxicity (ADCC). The binding characteristics of CBA-1205 were analyzed by enzyme-linked immunosorbent assay and fluorescence-activated cell sorting assay.
View Article and Find Full Text PDFA Critical Review on microRNAs as Prognostic Biomarkers in Laryngeal Carcinoma.
Int J Mol Sci
December 2024
Department of ENT, Medical University, 1000 Sofia, Bulgaria.
During the past decade, a vast number of studies were dedicated to unravelling the obscurities of non-coding RNAs in all fields of the medical sciences. A great amount of data has been accumulated, and consequently a natural need for organization and classification in all subfields arises. The aim of this review is to summarize all reports on microRNAs that were delineated as prognostic biomarkers in laryngeal carcinoma.
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!