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Gene Review

CDH2  -  cadherin 2, type 1, N-cadherin (neuronal)

Gallus gallus

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Disease relevance of CDH2


Psychiatry related information on CDH2


High impact information on CDH2


Chemical compound and disease context of CDH2


Biological context of CDH2

  • Similarly, this promoter fragment directed variable, but neuronal-specific, expression of reporter genes in adult transgenic mice, but failed to produce the correct pattern of expression in other tissues, implying that additional sequences further upstream and/or within introns of CDH2 may play important roles in the transcriptional control [10].
  • To investigate mechanisms controlling CDH2 transcription, we isolated and analyzed a genomic DNA sequence containing 2.8 kb of 5' flanking region and the first two exons of chicken CDH2 [10].
  • We report here the nucleotide sequence of the chicken N-cadherin cDNA and the deduced amino acid sequence [11].
  • Multiple N-cadherin enhancers identified by systematic functional screening indicate its Group B1 SOX-dependent regulation in neural and placodal development [12].
  • A 219-kb region of the chicken genome centered by the N-cadherin gene was scanned for neural and placodal enhancers [12].

Anatomical context of CDH2


Associations of CDH2 with chemical compounds

  • Since N-cadherin and integrin beta 1 antibodies together virtually eliminated E8 CG neurite outgrowth on cultured astrocytes, these two neuronal receptors are probably important in regulating axon growth on astroglia in vivo [2].
  • N-cadherin-induced neuronal Ca2+ responses are sensitive to Ni2+, but are relatively insensitive to diltiazem and omega-conotoxin [4].
  • Concomitant with inhibition of cadherin mediated adhesion, binding of the 250-kD core protein to the GalNAcPTase on cells results in the enhanced tyrosine phosphorylation of beta-catenin and the uncoupling of N-cadherin from its association with the cytoskeleton [14].
  • Similarly, anti-transferase antibodies immunoprecipitate N-cadherin containing complexes prior to disruption of the complex with sodium dodecyl sulfate [15].
  • Glycosylation of N-cadherin by the transferase also occurs in situ; labeling of retina cells with [32P] orthophosphate results in N-cadherin molecules containing terminal N-acetylgalactosamine linked to an oligosaccharide chain via a phosphodiester bond [15].

Physical interactions of CDH2


Enzymatic interactions of CDH2


Co-localisations of CDH2


Regulatory relationships of CDH2

  • The motor neurites expressing R-cadherin have a different course within the brain than the sensory neurites expressing N-cadherin, although they form the common sensory/motor roots of the vagus nerve at the surface of the brain [1].
  • When BHK cells were cultured as three-dimensional aggregates, N-cadherin enhanced withdrawal from the cell cycle and stimulated differentiation into skeletal muscle as measured by increased expression of sarcomeric myosin and the 12/101 antigen [20].
  • RT-PCR using mRNAs extracted from cardiac tubes revealed that the GATA-4-specific siRNA selectively suppresses expression of N-cadherin mRNA, one of the genes essential for the single heart formation, without affecting other cardiac marker mRNAs [18].
  • Catalytically inactive PIP5KIgamma or a cell-permeant peptide that mimics and competes for the PI(4,5)P2-binding region of the actin-binding protein gelsolin inhibited incorporation of actin monomers in response to N-cadherin ligation and reduced intercellular adhesion strength by more than twofold [21].

Other interactions of CDH2

  • In the neural tube, R-cadherin appears at around stage 21, although N-cadherin expression begins at a much earlier stage [22].
  • Neural plate and sensory placodes share the expression of N-cadherin and Group B1 Sox genes, represented by Sox2 [12].
  • We then compared the primary structure of N-cadherin with that of other molecules defined as cadherin subclasses [11].
  • Cotransfection of beta-catenin and LEF-1 into Chinese hamster ovary cells induced transactivation of a LEF-1 reporter, which was blocked by the N-cadherin-derived molecules [23].
  • Using computer-aided three-dimensional microscopy confirmed that these vinculin- and N-cadherin-containing structures are located in extrajunctional sites, apparently associated with Z-disks of peripheral myofibrils [24].

Analytical, diagnostic and therapeutic context of CDH2

  • To examine the influence of CAM expression on such cell segregation events in vitro, we have transfected cells with cDNAs coding for two calcium-dependent CAMs of different specificity, the liver CAM (L-CAM) and the structurally related molecule N-cadherin [25].
  • Denervation led to the renewed expression of N-cadherin in twitch fibers as well as a marked increase in expression in tonic fibers [6].
  • Immunoelectron microscopy of normal tecta demonstrated the presence of N-cadherin in the synaptic cleft, suggesting a role for this molecule in synaptic maintenance [26].
  • Antibodies prepared against N-cadherin precipitate the transferase containing complexes from neutral detergent extracts; however, when the complexes are dissociated by treatment with sodium dodecyl sulfate prior to immunoprecipitation, only N-cadherin is precipitated [15].
  • Ectopic expression of chicken N-cadherin in adult rat cardiomyocytes (ARC) in culture was obtained after microinjection into non-dividing cardiomyocytes; it was demonstrated that the exogenous protein colocalized with the endogenous N-cadherin at the plasma membrane of the cell and formed contact sites [27].


  1. Restricted expression of N- and R-cadherin on neurites of the developing chicken CNS. Redies, C., Inuzuka, H., Takeichi, M. J. Neurosci. (1992) [Pubmed]
  2. N-cadherin and integrins: two receptor systems that mediate neuronal process outgrowth on astrocyte surfaces. Tomaselli, K.J., Neugebauer, K.M., Bixby, J.L., Lilien, J., Reichardt, L.F. Neuron (1988) [Pubmed]
  3. cDNAs of cell adhesion molecules of different specificity induce changes in cell shape and border formation in cultured S180 cells. Matsuzaki, F., Mège, R.M., Jaffe, S.H., Friedlander, D.R., Gallin, W.J., Goldberg, J.I., Cunningham, B.A., Edelman, G.M. J. Cell Biol. (1990) [Pubmed]
  4. Ca2+ influx and neurite growth in response to purified N-cadherin and laminin. Bixby, J.L., Grunwald, G.B., Bookman, R.J. J. Cell Biol. (1994) [Pubmed]
  5. L-CAM expression induces fibroblast-epidermoid transition in squamous carcinoma cells and down-regulates the endogenous N-cadherin. Li, Z., Gallin, W.J., Lauzon, G., Pasdar, M. J. Cell. Sci. (1998) [Pubmed]
  6. Neural regulation of N-cadherin gene expression in developing and adult skeletal muscle. Hahn, C.G., Covault, J. J. Neurosci. (1992) [Pubmed]
  7. Guidance of optic nerve fibres by N-cadherin adhesion molecules. Matsunaga, M., Hatta, K., Nagafuchi, A., Takeichi, M. Nature (1988) [Pubmed]
  8. Role of N-cadherin cell adhesion molecules in the histogenesis of neural retina. Matsunaga, M., Hatta, K., Takeichi, M. Neuron (1988) [Pubmed]
  9. Purified N-cadherin is a potent substrate for the rapid induction of neurite outgrowth. Bixby, J.L., Zhang, R. J. Cell Biol. (1990) [Pubmed]
  10. Isolation and characterization of the promoter region of the chicken N-cadherin gene. Li, B., Paradies, N.E., Brackenbury, R.W. Gene (1997) [Pubmed]
  11. Cloning and expression of cDNA encoding a neural calcium-dependent cell adhesion molecule: its identity in the cadherin gene family. Hatta, K., Nose, A., Nagafuchi, A., Takeichi, M. J. Cell Biol. (1988) [Pubmed]
  12. Multiple N-cadherin enhancers identified by systematic functional screening indicate its Group B1 SOX-dependent regulation in neural and placodal development. Matsumata, M., Uchikawa, M., Kamachi, Y., Kondoh, H. Dev. Biol. (2005) [Pubmed]
  13. Neural crest emigration from the neural tube depends on regulated cadherin expression. Nakagawa, S., Takeichi, M. Development (1998) [Pubmed]
  14. The interaction of the retina cell surface N-acetylgalactosaminylphosphotransferase with an endogenous proteoglycan ligand results in inhibition of cadherin-mediated adhesion. Balsamo, J., Ernst, H., Zanin, M.K., Hoffman, S., Lilien, J. J. Cell Biol. (1995) [Pubmed]
  15. N-cadherin is stably associated with and is an acceptor for a cell surface N-acetylgalactosaminylphosphotransferase. Balsamo, J., Lilien, J. J. Biol. Chem. (1990) [Pubmed]
  16. Assembly of the N-cadherin complex during synapse formation involves uncoupling of p120-catenin and association with presenilin 1. Rubio, M.E., Curcio, C., Chauvet, N., Brusés, J.L. Mol. Cell. Neurosci. (2005) [Pubmed]
  17. Differential expression of endothelial beta-catenin and plakoglobin during development and maturation of the blood-brain and blood-retina barrier in the chicken. Liebner, S., Gerhardt, H., Wolburg, H. Dev. Dyn. (2000) [Pubmed]
  18. GATA-4 regulates cardiac morphogenesis through transactivation of the N-cadherin gene. Zhang, H., Toyofuku, T., Kamei, J., Hori, M. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  19. N-cadherin/catenin-based costameres in cultured chicken cardiomyocytes. Wu, J.C., Chung, T.H., Tseng, Y.Z., Wang, S.M. J. Cell. Biochem. (1999) [Pubmed]
  20. Cadherins promote skeletal muscle differentiation in three-dimensional cultures. Redfield, A., Nieman, M.T., Knudsen, K.A. J. Cell Biol. (1997) [Pubmed]
  21. Phosphatidylinositol-4,5 bisphosphate produced by PIP5KIgamma regulates gelsolin, actin assembly, and adhesion strength of N-cadherin junctions. El Sayegh, T.Y., Arora, P.D., Ling, K., Laschinger, C., Janmey, P.A., Anderson, R.A., McCulloch, C.A. Mol. Biol. Cell (2007) [Pubmed]
  22. Differential expression of R- and N-cadherin in neural and mesodermal tissues during early chicken development. Inuzuka, H., Redies, C., Takeichi, M. Development (1991) [Pubmed]
  23. Inhibition of beta-catenin-mediated transactivation by cadherin derivatives. Sadot, E., Simcha, I., Shtutman, M., Ben-Ze'ev, A., Geiger, B. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  24. The involvement of adherens junction components in myofibrillogenesis in cultured cardiac myocytes. Goncharova, E.J., Kam, Z., Geiger, B. Development (1992) [Pubmed]
  25. Cell sorting-out is modulated by both the specificity and amount of different cell adhesion molecules (CAMs) expressed on cell surfaces. Friedlander, D.R., Mège, R.M., Cunningham, B.A., Edelman, G.M. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  26. Lamina-specific expression of adhesion molecules in developing chick optic tectum. Yamagata, M., Herman, J.P., Sanes, J.R. J. Neurosci. (1995) [Pubmed]
  27. N-cadherin in adult rat cardiomyocytes in culture. I. Functional role of N-cadherin and impairment of cell-cell contact by a truncated N-cadherin mutant. Hertig, C.M., Eppenberger-Eberhardt, M., Koch, S., Eppenberger, H.M. J. Cell. Sci. (1996) [Pubmed]
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