Disease relevance of Notch1

• Effect of experimental varicocele on the expressions of Notch 1, 2, and 3 in rat testes: an immunohistochemical study [1].
• We studied the consequences of supplying excess Notch1 signal in vivo on the cellular and regional destinies of telencephalic precursors using bicistronic replication defective retroviruses [2].
• Furthermore, overexpression of a constitutively active form of Notch1 inhibited the proliferation of various prostate cancer cells, including DU145, LNCaP, and PC3 cells [3].
• Examination of the transgenic adenocarcinoma of the mouse prostate showed that expression of Notch1 was elevated in malignant prostatic epithelial cells of primary and metastatic tumors [3].
• Thus, the NB-3/Notch signaling pathway may prove to be a molecular handle to treat demyelinating diseases [4].

High impact information on Notch1

• Possible intracellular transduction events mediating signals from Notch are, however, unknown. shaggy is also required for the lateral signal and encodes serine/threonine protein kinases with homology to the glycogen synthase kinase-3 (GSK-3) enzymes that act in signal transduction pathways in vertebrates [5].
• Accordingly, transient ectopic expression of activated Notch1 (N1IC) in zebrafish embryos leads to hypercellular cardiac valves, whereas Notch inhibition prevents valve development [6].
• The Lin12/Notch receptors regulate cell fate during embryogenesis by activating the expression of downstream target genes [7].
• Notch1 cytoplasmic-domain constructs transfected into cortical neurons were present in multiple phosphorylated forms, localized to the nucleus and could induce CBF1-mediated transactivation [8].
• Here we present evidence that activated Notch1 and Notch3 promotes the differentiation of astroglia from the rat adult hippocampus-derived multipotent progenitors (AHPs) [9].

Biological context of Notch1

• Within zones of cellular proliferation of the postnatal brain, Notch1 mRNA is found in both the subventricular and the ventricular germinal zones, whereas Notch2 and Notch3 mRNAs are more highly localized to the ventricular zones [10].
• Our data suggest that the Notch1 signaling pathway is involved in a complex interplay between the consequences of different ligand-Notch1 combinations during cochlear morphogenesis and the phases of hair cell differentiation [11].
• The Notch1 pathway plays a fundamental role during the establishment of cell fates in the central nervous system (CNS) by regulating neural cell differentiation [12].
• In this study, we have found that Notch1 gene expression was higher in proliferative OL progenitor cells (OPCs) and was reduced when cells were forced to withdraw from the cell cycle and became mature, indicating that Notch1 gene expression is developmentally regulated in OLs [12].
• This suggests that a downregulation of the Notch1 pathway might be required to allow OPCs to enter terminal differentiation [12].

Anatomical context of Notch1

• Neurosphere cultures (which contain CNS stem cells), purified astrocyte cultures, and striatal neuron-enriched cultures express Notch1 mRNA [10].
• Both Notch1 and Notch3 mRNAs are expressed along the inner aspect of the dentate gyrus, a site of adult neurogenesis [10].
• CONCLUSION(S): The present study suggests that Notch 1 is related to the maturation of spermatids [1].
• RESULT(S): In the sham-operation rat testes, Leydig cells and elongated spermatids were immunopositive for Notch 1 [1].
• Notch1 has been shown to induce glia in the peripheral nervous system [9].

Associations of Notch1 with chemical compounds

• We observed that the blockade of terminal differentiation of OPCs by incubation with Delta1, an activator of Notch1, was a dominant process and OL-differentiating signals such as thyroid hormone could not overcome this inhibition in culture [12].
• The protein quality of high lysine barley genotypes Notch1 Notch2, Riso-1508 and Hiproly grown in Indian soil was evaluated by determining amino acid composition and also by rat growth and nitrogen balance studies [13].
• We have shown previously that Notch1 regulates the molecular and morphological differentiation of radial glia through the transcriptional activation of at least two genes, brain lipid binding protein (BLBP) and the erbB2 receptor tyrosine kinase [14].

Physical interactions of Notch1

• Recent data suggest that Notch receptors and their membrane-bound ligands Delta and Serrate are involved in both patterning and cell fate determination during odontogenesis [15].

Regulatory relationships of Notch1

• Some ALP-positive cells were almost consistent with Notch1-expressing cells but not Jagged1-expressing cells [16].
• First, Notch1 activation by neuronal contact induces the glial expression of the brain lipid binding protein (BLBP) and erbB2 genes [17].
• Notch1 was preferentially expressed in cholinergic neurons lacking calretinin or nitric oxide synthase (NOS), whereas Jagged2 was present in most neuron subtypes [18].
• Taken together, these data suggest that basal IkappaBalpha expression (and as a consequence NF-kappaB activity) is under the control of the various components of the CBF1/Notch signal transduction pathway [19].
• Transfection of insulin-producing INS-1E cells and primary rat beta-cells with a constitutively active form of the Notch receptor down-regulated Pdx1 and insulin expression in INS-1E cells but not in primary beta-cells [20].

Other interactions of Notch1

• In several brain areas, Notch1 and Notch2 mRNAs are relatively concentrated in white matter, whereas Notch3 mRNA is not [10].
• However, in these latter cultures, Notch1 mRNA is produced by nestin-containing cells, rather than by postmitotic neurons [10].
• A decrease of either Notch1 or Jag1 expression by antisense oligonucleotides in cultures of the developing sensory epithelium resulted in an increase in the number of hair cells [11].
• We also provide evidence that OPCs and OLs express the Numb gene, a known negative regulator of Notch1 activity [12].
• Early after birth, Jag2 expression decreased in hair cells while the pattern of Notch1 expression now included both supporting cells and hair cells [11].

Analytical, diagnostic and therapeutic context of Notch1

• In the current study, we examined the expression patterns for three receptors of this system, Notch1, 2, and 3, in late embryonic and postnatal rat brain by in situ hybridization [10].
• In injured teeth, Notch2 was expressed in mesenchymal cells of the pulp both close to the site of injury (i.e., in the dental crown) and at a distance from it (i.e., in the dental roots), Notch3 expression was mainly associated with vascular structures, while Notch1 expression was restricted to few pulpal cells close to the lesion [15].
• In this study we explored Notch signaling after the pulp capping of adult first upper rat molars [21].
• Similarly, in thymic lobes reconstituted with fetal liver cells, progenitors predominantly develop into NK cells both after pharmacological interference of Notch and after treatment with a recombinant rat Notch1/Fc chimera [22].
• (3) Notch receptor-soluble jagged1 protein was added to indirect coculture group [23].

References