Notch Signaling and Cell Fate Determination in the Vertebrate Inner Ear

2006 ◽  
pp. 122-157 ◽  
Author(s):  
Pamela J. Lanford ◽  
Matthew W. Kelley
Keyword(s):  
Notch Signaling ◽  
Inner Ear ◽  
Cell Fate ◽  
Cell Fate Determination ◽  
Fate Determination

scholarly journals Jagged–Delta asymmetry in Notch signaling can give rise to a Sender/Receiver hybrid phenotype

2015 ◽  
Vol 112 (5) ◽  
pp. E402-E409 ◽  
Author(s):  
Marcelo Boareto ◽  
Mohit Kumar Jolly ◽  
Mingyang Lu ◽  
José N. Onuchic ◽  
Cecilia Clementi ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Cell Fate ◽  
Target Genes ◽  
Tumor Stroma ◽  
Notch Receptor ◽  
Toggle Switch ◽  
Cell Fate Determination ◽  
Asymmetric Effect ◽  
Fate Determination

Notch signaling pathway mediates cell-fate determination during embryonic development, wound healing, and tumorigenesis. This pathway is activated when the ligand Delta or the ligand Jagged of one cell interacts with the Notch receptor of its neighboring cell, releasing the Notch Intracellular Domain (NICD) that activates many downstream target genes. NICD affects ligand production asymmetrically––it represses Delta, but activates Jagged. Although the dynamical role of Notch–Jagged signaling remains elusive, it is widely recognized that Notch–Delta signaling behaves as an intercellular toggle switch, giving rise to two distinct fates that neighboring cells adopt––Sender (high ligand, low receptor) and Receiver (low ligand, high receptor). Here, we devise a specific theoretical framework that incorporates both Delta and Jagged in Notch signaling circuit to explore the functional role of Jagged in cell-fate determination. We find that the asymmetric effect of NICD renders the circuit to behave as a three-way switch, giving rise to an additional state––a hybrid Sender/Receiver (medium ligand, medium receptor). This phenotype allows neighboring cells to both send and receive signals, thereby attaining similar fates. We also show that due to the asymmetric effect of the glycosyltransferase Fringe, different outcomes are generated depending on which ligand is dominant: Delta-mediated signaling drives neighboring cells to have an opposite fate; Jagged-mediated signaling drives the cell to maintain a similar fate to that of its neighbor. We elucidate the role of Jagged in cell-fate determination and discuss its possible implications in understanding tumor–stroma cross-talk, which frequently entails Notch–Jagged communication.

scholarly journals Competition and collaboration: GATA-3, PU.1, and Notch signaling in early T-cell fate determination

2008 ◽  
Vol 20 (4) ◽  
pp. 236-246 ◽  
Author(s):  
Ellen V. Rothenberg ◽  
Deirdre D. Scripture-Adams
Keyword(s):  
T Cell ◽  
Notch Signaling ◽  
Cell Fate ◽  
Cell Fate Determination ◽  
Fate Determination

scholarly journals Notch Signaling in Vascular Endothelial Cells, Angiogenesis, and Tumor Progression: An Update and Prospective

2021 ◽  
Vol 9 ◽  
Author(s):  
Abdellah Akil ◽  
Ana K. Gutiérrez-García ◽  
Rachael Guenter ◽  
J. Bart Rose ◽  
Adam W. Beck ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tumor Progression ◽  
Notch Signaling ◽  
Cell Fate ◽  
Tumor Angiogenesis ◽  
Vascular Endothelial Cells ◽  
Notch Pathway ◽  
Vascular Endothelial ◽  
Cell Fate Determination ◽  
Fate Determination

The Notch signaling pathway plays an essential role in a wide variety of biological processes including cell fate determination of vascular endothelial cells and the regulation of arterial differentiation and angiogenesis. The Notch pathway is also an essential regulator of tumor growth and survival by functioning as either an oncogene or a tumor suppressor in a context-dependent manner. Crosstalk between the Notch and other signaling pathways is also pivotal in tumor progression by promoting cancer cell growth, migration, invasion, metastasis, tumor angiogenesis, and the expansion of cancer stem cells (CSCs). In this review, we provide an overview and update of Notch signaling in endothelial cell fate determination and functioning, angiogenesis, and tumor progression, particularly in the development of CSCs and therapeutic resistance. We further summarize recent studies on how endothelial signaling crosstalk with the Notch pathway contributes to tumor angiogenesis and the development of CSCs, thereby providing insights into vascular biology within the tumor microenvironment and tumor progression.

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