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Gene Review

Notch1  -  notch 1

Rattus norvegicus

Synonyms: NOTCH, Neurogenic locus notch homolog protein 1, Notch 1, TAN1
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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


Anatomical context of Notch1


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].


  1. Effect of experimental varicocele on the expressions of Notch 1, 2, and 3 in rat testes: an immunohistochemical study. Sahin, Z., Bayram, Z., Celik-Ozenci, C., Akkoyunlu, G., Seval, Y., Erdogru, T., Ustunel, I., Baykara, M., Demir, R. Fertil. Steril. (2005) [Pubmed]
  2. Spatiotemporal selectivity of response to Notch1 signals in mammalian forebrain precursors. Chambers, C.B., Peng, Y., Nguyen, H., Gaiano, N., Fishell, G., Nye, J.S. Development (2001) [Pubmed]
  3. Dynamics of notch expression during murine prostate development and tumorigenesis. Shou, J., Ross, S., Koeppen, H., de Sauvage, F.J., Gao, W.Q. Cancer Res. (2001) [Pubmed]
  4. NB-3/Notch1 pathway via Deltex1 promotes neural progenitor cell differentiation into oligodendrocytes. Cui, X.Y., Hu, Q.D., Tekaya, M., Shimoda, Y., Ang, B.T., Nie, D.Y., Sun, L., Hu, W.P., Karsak, M., Duka, T., Takeda, Y., Ou, L.Y., Dawe, G.S., Yu, F.G., Ahmed, S., Jin, L.H., Schachner, M., Watanabe, K., Arsenijevic, Y., Xiao, Z.C. J. Biol. Chem. (2004) [Pubmed]
  5. Drosophila shaggy kinase and rat glycogen synthase kinase-3 have conserved activities and act downstream of Notch. Ruel, L., Bourouis, M., Heitzler, P., Pantesco, V., Simpson, P. Nature (1993) [Pubmed]
  6. Notch promotes epithelial-mesenchymal transition during cardiac development and oncogenic transformation. Timmerman, L.A., Grego-Bessa, J., Raya, A., Bertrán, E., Pérez-Pomares, J.M., Díez, J., Aranda, S., Palomo, S., McCormick, F., Izpisúa-Belmonte, J.C., de la Pompa, J.L. Genes Dev. (2004) [Pubmed]
  7. Nrarp is a novel intracellular component of the Notch signaling pathway. Lamar, E., Deblandre, G., Wettstein, D., Gawantka, V., Pollet, N., Niehrs, C., Kintner, C. Genes Dev. (2001) [Pubmed]
  8. Nuclear Notch1 signaling and the regulation of dendritic development. Redmond, L., Oh, S.R., Hicks, C., Weinmaster, G., Ghosh, A. Nat. Neurosci. (2000) [Pubmed]
  9. Notch1 and Notch3 instructively restrict bFGF-responsive multipotent neural progenitor cells to an astroglial fate. Tanigaki, K., Nogaki, F., Takahashi, J., Tashiro, K., Kurooka, H., Honjo, T. Neuron (2001) [Pubmed]
  10. Expression patterns of Notch1, Notch2, and Notch3 suggest multiple functional roles for the Notch-DSL signaling system during brain development. Irvin, D.K., Zurcher, S.D., Nguyen, T., Weinmaster, G., Kornblum, H.I. J. Comp. Neurol. (2001) [Pubmed]
  11. Notch signaling regulates the pattern of auditory hair cell differentiation in mammals. Zine, A., Van De Water, T.R., de Ribaupierre, F. Development (2000) [Pubmed]
  12. Notch1 and Numb genes are inversely expressed as oligodendrocytes differentiate. Givogri, M.I., Schonmann, V., Cole, R., De Vellis, J., Bongarzone, E.R. Dev. Neurosci. (2003) [Pubmed]
  13. Amino acid composition and biological evaluation of the protein quality of high lysine barley genotypes. Jood, S., Singh, M. Plant foods for human nutrition (Dordrecht, Netherlands) (2001) [Pubmed]
  14. Notch1 signaling regulates radial glia differentiation through multiple transcriptional mechanisms. Patten, B.A., Sardi, S.P., Koirala, S., Nakafuku, M., Corfas, G. J. Neurosci. (2006) [Pubmed]
  15. Reactivation of Delta-Notch signaling after injury: complementary expression patterns of ligand and receptor in dental pulp. Mitsiadis, T.A., Fried, K., Goridis, C. Exp. Cell Res. (1999) [Pubmed]
  16. Establishment of dental epithelial cell line (HAT-7) and the cell differentiation dependent on Notch signaling pathway. Kawano, S., Morotomi, T., Toyono, T., Nakamura, N., Uchida, T., Ohishi, M., Toyoshima, K., Harada, H. Connect. Tissue Res. (2002) [Pubmed]
  17. Sequential signaling through Notch1 and erbB receptors mediates radial glia differentiation. Patten, B.A., Peyrin, J.M., Weinmaster, G., Corfas, G. J. Neurosci. (2003) [Pubmed]
  18. Expression of Notch1 and Jagged2 in the enteric nervous system. Sander, G.R., Brookes, S.J., Powell, B.C. J. Histochem. Cytochem. (2003) [Pubmed]
  19. Basal expression of IkappaBalpha is controlled by the mammalian transcriptional repressor RBP-J (CBF1) and its activator Notch1. Oakley, F., Mann, J., Ruddell, R.G., Pickford, J., Weinmaster, G., Mann, D.A. J. Biol. Chem. (2003) [Pubmed]
  20. Notch signaling: a mediator of beta-cell de-differentiation in diabetes? Darville, M.I., Eizirik, D.L. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  21. Activation of the Notch signaling pathway in response to pulp capping of rat molars. Løvschall, H., Tummers, M., Thesleff, I., Füchtbauer, E.M., Poulsen, K. Eur. J. Oral Sci. (2005) [Pubmed]
  22. Inhibition of Notch signaling biases rat thymocyte development towards the NK cell lineage. van den Brandt, J., Voss, K., Schott, M., Hünig, T., Wolfe, M.S., Reichardt, H.M. Eur. J. Immunol. (2004) [Pubmed]
  23. Jagged1 protein enhances the differentiation of mesenchymal stem cells into cardiomyocytes. Li, H., Yu, B., Zhang, Y., Pan, Z., Xu, W., Li, H. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
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