Notch signaling pathway

NotchNotch signalingNotch receptorNotch pathwayNotch signalling pathwayDeltaNotch ligandNotch signallingDelta (ligand)Delta ligand
The Notch signaling pathway is a highly conserved cell signaling system present in most animals.wikipedia
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Notch 1

NOTCH1Notch-1
Mammals possess four different notch receptors, referred to as NOTCH1, NOTCH2, NOTCH3, and NOTCH4.
This gene encodes a member of the Notch family.

Notch proteins

NotchNotch proteinNotch receptors
Mammals possess four different notch receptors, referred to as NOTCH1, NOTCH2, NOTCH3, and NOTCH4.
Notch proteins are a family of type-1 transmembrane proteins that form a core component of the Notch signaling pathway, which is highly conserved in metazoans.

Notch 2

NOTCH2Notch-2
Mammals possess four different notch receptors, referred to as NOTCH1, NOTCH2, NOTCH3, and NOTCH4.
Notch 2 is a member of the notch family.

NUMB (gene)

NUMBNotch-binding protein
Notch signaling promotes proliferative signaling during neurogenesis, and its activity is inhibited by Numb to promote neural differentiation.
Numb’s primary function in cell differentiation is as an inhibitor of Notch signaling which is essential for maintaining self-renewal potential in stem and progenitor cells.

Caenorhabditis elegans

C. eleganswormsC.elegans
Alleles of the two C. elegans Notch genes were identified based on developmental phenotypes: lin-12 and glp-1.
Through Notch signaling, the P2 cell differentially specifies the ABp and ABa cells, which further defines the dorsal-ventral axis.

JAG1

Jagged1CD339Jagged
In mammals, the corresponding names are Delta-like and Jagged.
Jagged1 (JAG1) is one of five cell surface proteins (ligands) that interact with 4 receptors in the mammalian Notch signaling pathway.

Neurogenic locus notch homolog protein 4

NOTCH4
Mammals possess four different notch receptors, referred to as NOTCH1, NOTCH2, NOTCH3, and NOTCH4.
The Notch signaling pathway is an evolutionarily conserved intercellular signaling pathway that regulates interactions between physically adjacent cells

RBPJ

CBF1RBP-JKRBP-Jκ
The intracellular domain of Notch forms a complex with CBF1 and Mastermind to activate transcription of target genes. This releases the intracellular domain of the notch protein (NICD), which then moves to the nucleus, where it can regulate gene expression by activating the transcription factor CSL.
Its promoter region is classically used to demonstrate Notch1 signaling.

Fringe gene

Fringefringe genesRadical Fringe
The O-glucose on notch can be further elongated to a trisaccharide with the addition of two xylose sugars by xylosyltransferases, and the O-fucose can be elongated to a tetrasaccharide by the ordered addition of an N-acetylglucosamine (GlcNAc) sugar by an N-Acetylglucosaminyltransferase called Fringe, the addition of a galactose by a galactosyltransferase, and the addition of a sialic acid by a sialyltransferase.
Fringe genes are important in the workings of the notch signaling pathway.

Rex1

ZFP42
It has also been found that Rex1 has inhibitory effects on the expression of notch in mesenchymal stem cells, preventing differentiation.
Rex1 was also found to inhibit NOTCH and STAT3, two transcription factors which lead to differentiation.

Pancreas

pancreaticexocrine pancreaspancreatic development
In cells of the exocrine pancreas, important molecules that induce differentiation include follistatin, fibroblast growth factors, and activation of the Notch receptor system.

Alagille syndrome

Alagille's syndromeAlagille–Watson syndrome (AWS)
Notch signaling is dysregulated in many cancers, and faulty notch signaling is implicated in many diseases including T-ALL (T-cell acute lymphoblastic leukemia), CADASIL (Cerebral Autosomal-Dominant Arteriopathy with Sub-cortical Infarcts and Leukoencephalopathy), multiple sclerosis (MS), Tetralogy of Fallot, Alagille syndrome, and many other disease states.
JAG1 and NOTCH2 encode for proteins that are crucial to the notch gene–signaling cascade.

Angiogenesis

angiogenicvascularizationvascularized
Endothelial cells use the Notch signaling pathway to coordinate cellular behaviors during the blood vessel sprouting that occurs in angiogenesis.
Dll4 is a transmembrane ligand, for the notch family of receptors.

GDP-fucose protein O-fucosyltransferase 1

GDP-fucose Protein ''O''-fucosyltransferase 1O''-fucosyltransferasePOFUT1
These sugars are added by an as-yet-unidentified O-glucosyltransferase (except for Rumi), and GDP-fucose Protein O-fucosyltransferase 1 (POFUT1), respectively.
When the gene for POFUT1 is knocked out, or the expression is decreased to very low levels, all Notch signaling is destroyed, which means that fucose on Notch is essential for Notch function.

Somite

somitessclerotomedermatome
For example, mutation experiments have shown that loss of Notch signaling causes abnormal anterior-posterior polarity in somites. A clock and wavefront model has been proposed in order to spatially determine the location and boundaries between somites.
In one description of the model, oscillating Notch and Wnt signals provide the clock.

Glycan

glycansN-linked GlycanN-linked glycans
Each EGF-like repeat can be modified by O-linked glycans at specific sites.

Hes3 signaling axis

Hes3STAT3-Ser/Hes3 Signaling Axis
A non-canonical branch of the Notch signaling pathway that involves the phosphorylation of STAT3 on the serine residue at amino acid position 727 and subsequent Hes3 expression increase (STAT3-Ser/Hes3 Signaling Axis) has been shown to regulate the number of NPCs in culture and in the adult rodent brain.
The notch/STAT3-Ser/Hes3 signaling axis is a recently identified signal transduction branch of the notch signaling pathway, originally shown to regulate the number of neural stem cells in culture and in the living adult brain.

PSEN2

presenilin 2presenilin-2
Furthermore, it has found that presenilin-2 works in conjunction with ARF4 to regulate Notch signaling during this development.
Also, it is thought that the presenilins are involved in the cleavage of the Notch receptor, such that they either directly regulate gamma-secretase activity or themselves are protease enzymes.

Gamma secretase

γ-secretasegamma-secretaseγ-secretases
After this first cleavage, an enzyme called γ-secretase (which is implicated in Alzheimer's disease) cleaves the remaining part of the notch protein just inside the inner leaflet of the cell membrane of the notch-expressing cell.
Gamma secretase is also critical in the related processing of several other type I integral membrane proteins, such as Notch, ErbB4, E-cadherin, N-cadherin, ephrin-B2, or CD44.

Somitogenesis

truncation of embryonic structures
Notch signaling is central to somitogenesis.
These genes include members of the FGF family, Wnt and Notch pathway, as well as targets of these pathways.

Gliogenesis

In gliogenesis, Notch appears to have an instructive role that can directly promote the differentiation of many glial cell subtypes.
The Notch family proteins are transmembrane receptors that are ligand activated.

Transcription factor

transcription factorsgene transcription factortranscriptional factors
This releases the intracellular domain of the notch protein (NICD), which then moves to the nucleus, where it can regulate gene expression by activating the transcription factor CSL.
Transcription factors outside the nuclear receptor family are thought to be more difficult to target with small molecule therapeutics since it is not clear that they are "drugable" but progress has been made on Pax2 and the notch pathway.

Clock and wavefront model

clock and wave" mechanism
A clock and wavefront model has been proposed in order to spatially determine the location and boundaries between somites.
These genes include members of the FGF family, Wnt and Notch pathway, as well as targets of these pathways.

HEY2

The expression of the Hey2 gene is induced by the Notch signaling pathway.

Cerebral cortex

cortexcorticalsubcortical
Conversely, the fibroblast growth factor pathway promotes Notch signaling to keep stem cells of the cerebral cortex in the proliferative state, amounting to a mechanism regulating cortical surface area growth and, potentially, gyrification.
Rapid expansion of the cortical surface area is regulated by the amount of self-renewal of radial glial cells and is partly regulated by FGF and Notch genes.