Notch signaling is essential for vascular morphogenesis in mice.
By Luke T. Krebs, Yingzi Xue, C. Norton, J. Shutter, M. Maguire, J. Sundberg, D. Gallahan, V. Closson, J. Kitajewski, R. Callahan and 3 more. Genes & Development, 2000
1,121 citations recorded by the source corpus.
The Notch gene family encodes large transmembrane receptors that are components of an evolutionarily conserved intercellular signaling mechanism. To assess the role of the Notch4 gene, we generated Notch4-deficient mice by gene targeting. Embryos homozygous for this mutation developed normally, and homozygous mutant adults were viable and fertile. However, the Notch4 mutation displayed genetic interactions with a targeted mutation of the related Notch1 gene. Embryos homozygous for mutations of both the Notch4 and Notch1 genes often displayed a more severe phenotype than Notch1 homozygous mutant embryos. Both Notch1 mutant and Notch1/Notch4 double mutant embryos displayed severe defects in angiogenic vascular remodeling. Analysis of the expression patterns of genes encoding ligands for Notch family receptors indicated that only the Dll4 gene is expressed in a pattern consistent with that expected for a gene encoding a ligand for the Notch1 and Notch4 receptors in the early embryonic vasculature. These results reveal an essential role for the Notch signaling pathway in regulating embryonic vascular morphogenesis and remodeling, and indicate that whereas the Notch4 gene is not essential during embryonic development, the Notch4 and Notch1 genes have partially overlapping roles during embryogenesis in mice.
Subfields: Molecular Biology, Neurology
View Paper: https://www.semanticscholar.org/paper/81212493ccf22ce5531fa9b1b1fe724fef1c38c4
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Citations in the corpus
- Role of Notch signaling in cell-fate determination of human mammary stem/progenitor cells (2004, background): “Questions remain in interpreting the report that the Notch4 knockout mouse has no apparent defect in mammary gland development [31].”
- The disintegrin/metalloprotease ADAM 10 is essential for Notch signalling but not for alpha-secretase activity in fibroblasts. (2002, background): “Similar to other knockout models with a more generalized (notch-1/notch-4 double-knockout mice) or putatively total (PS1/2 double-knockout mice) inactivation of Notch signalling (44,45), yolk sacs of ADAM 10-deficient embryos featured enlarged extraembryonic blood vessels filled with large numbers o”
- Notch promotes epithelial-mesenchymal transition during cardiac development and oncogenic transformation. (2004, background): “Similarly, angiogenesis requires transient endothelial EMT, and Notch1; Notch4 double mutant embryos exhibit severe angiogenic abnormalities (Krebs et al. 2000), suggesting that Notch-mediated EMT may underlie this defect.”
- Adam10 is essential for early embryonic cardiovascular development (2010, background): “The AEKO mice not only phenocopied theNotch1 andNotch targets knockouts (Krebs et al., 2000; Fischer et al., 2004; Timmerman et al., 2004; Limbourg et al., 2005; Grego-Bessa et al., 2007), but also showed downregulated expression of Notch target gene Snail and Bmp2 in the cardiac tissues.”