Proto‐oncogene of int‐3, a mouse Notch homologue, is expressed in endothelial cells during early embryogenesis

Shirayoshi, Yasuaki; Yuasa, Y.; Suzuki, Takashi; Sugaya, Kimio; Kawase, Eihachiro; Ikemura, Toshimichi; Nakatsuji, Norio

doi:10.1046/j.1365-2443.1997.d01-310.x

Cited by 66 publications

(45 citation statements)

References 36 publications

(66 reference statements)

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“…Several isoforms of Notch are expressed in the developing vasculature (38), with Notch4 expression being restricted to cells of the endothelial lineage (39,40). Vascular remodeling deficits similar to those evident in Fbw7 Ϫ/Ϫ embryos have been observed in mice lacking Notch1, both Notch1 and Notch4 (7), Tie2 (41), or angiopoietin-1 (42) but not in Notch4 Ϫ/Ϫ embryos (7), suggesting that Notch1 compensates for the loss of function of Notch4.…”

Section: Discussionmentioning

confidence: 99%

“…Notch1 was recently shown to be a downstream effector of oncogenic Ras, and down-regulation of Notch1 in Ras-transformed human cells was sufficient to abolish key elements of the neoplastic phenotype in vitro and in vivo (60). Notch4 was also originally identified as Int3, a proto-oncogene that is a frequent target for integration of mouse mammary tumor virus in mammary carcinomas (39,40,61). Mutation of human FBW7 and an associated accumulation of cyclin E has been detected in various cancer cell lines (17,18).…”

Section: Discussionmentioning

confidence: 99%

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Mouse Fbw7/Sel-10/Cdc4 Is Required for Notch Degradation during Vascular Development

Tsunematsu

Nakayama

Oike

et al. 2004

Journal of Biological Chemistry

233

204

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Mammalian Fbw7 (also known as Sel-10, hCdc4, or hAgo) is the F-box protein component of an SCF (Skp1-Cul1-F-box protein-Rbx1)-type ubiquitin ligase, and the mouse Fbw7 is expressed prominently in the endothelial cell lineage of embryos. We generated mice deficient in Fbw7 and found that the embryos died in utero at embryonic day 10.5-11.5, manifesting marked abnormalities in vascular development. Vascular remodeling was impaired in the brain and yolk sac, and the major trunk veins were not formed. In vitro para-aortic splanchnopleural explant cultures from Fbw7 ؊/؊ embryos also manifested an impairment of vascular network formation. Notch4, which is the product of the proto-oncogene Int3 and an endothelial cell-specific mammalian isoform of Notch, accumulated in Fbw7 ؊/؊ embryos, resulting in an increased expression of Hey1, which encodes a transcriptional repressor that acts downstream of Notch signaling and is implicated in vascular development. Expression of Notch1, -2, or -3 or of cyclin E was unaffected in Fbw7 ؊/؊ embryos. Mammalian Fbw7 thus appears to play an indispensable role in negative regulation of the Notch4-Hey1 pathway and is required for vascular development.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Mouse Fbw7/Sel-10/Cdc4 Is Required for Notch Degradation during Vascular Development

Tsunematsu

Nakayama

Oike

et al. 2004

Journal of Biological Chemistry

233

204

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“…Notch3 has a more recent phylogenetic origin and has been identified only in mammals (Faux et al, 2001). Notch4 also has been shown only in mammals: since it diverges in many aspects from the others, its exclusion from the Notch family has been proposed (Lardelli et al, 1995;Shirayoshi et al, 1997).…”

mentioning

confidence: 99%

Physiology and pathology of notch signalling system

Bianchi

Dotti

Federico

2005

Journal Cellular Physiology

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Notch proteins encode a family of transmembrane receptors that are part of a signalling transduction system known as Notch signalling, an extremely conserved and widely used mechanism regulating programs governing growth, apoptosis and differentiation in metazoans. Notch signalling begins when the Notch receptor binds ligands and ends when the Notch intracellular domain enters the nucleus and activates transcription of target genes. This core pathway is subjected to a wide array of regulatory influences and protein-protein interactions and is correlated with other signalling pathway. This review will sumarize recent findings concerning the physiology and pathology of Notch signalling in vascular development and homeostasis. Moreover, the clinical phenotypes of Notch3 signalling system pathology will be described, with particular regard to CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) for which the most recent pathogenetic hypotheses are reported.

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“…To date, four Notch family receptors and five ligands have been described in mammals. Evidence that the Notch pathway plays a critical role in vascular development and homeostasis includes the specific expression of Notch pathway ligands and receptors in vascular endothelium or supporting cells (7)(8)(9)(10)(11)(12)(13)(14), as well as the phenotypes of several targeted mutants in Notch pathway components. These mutants, which include mutations in genes encoding both ligands and receptors, die during embryogenesis from hemorrhaging because of defects in vascular morphogenesis (15)(16)(17).…”

mentioning

confidence: 99%

Notch signaling during vascular development

Gridley

2001

Proc. Natl. Acad. Sci. U.S.A.

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**Proto‐oncogene of int‐3, a mouse Notch homologue, is expressed in endothelial cells during early embryogenesis**

Cited by 66 publications

References 36 publications

Mouse Fbw7/Sel-10/Cdc4 Is Required for Notch Degradation during Vascular Development

Mouse Fbw7/Sel-10/Cdc4 Is Required for Notch Degradation during Vascular Development

Physiology and pathology of notch signalling system

Notch signaling during vascular development

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