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Gene Review

Cntn2  -  contactin 2

Mus musculus

Synonyms: Axonal glycoprotein TAG-1, Axonin-1, Contactin-2, D130012K04Rik, TAG-1, ...
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Disease relevance of Cntn2


High impact information on Cntn2


Chemical compound and disease context of Cntn2


Biological context of Cntn2

  • We used carbocyanine dye tracing to visualize thalamocortical and corticofugal projections as well as immunohistochemistry for L1 and TAG-1, respective markers of the two axonal systems, in wild-type, heterozygote, and null mutant for Emx2 at embryonic (E) ages ranging from E13.5 to E18 [10].
  • These findings provide evidence that the TAG-1 protein is involved as a contact-dependent signal guiding not only axonal outgrowth but also cell migration [11].
  • The perturbation of each region alone resulted in a complete loss of cell aggregation, suggesting that axonin-1-mediated cell-cell contact results from a cooperative action of two homophilic binding regions [12].
  • In this report, we analyze the developmental phenotype of TAG-1-deficient animals in these two migratory systems [13].
  • However, TAG-1 (-/-) mice showed the upregulation of the adenosine A1 receptors determined by [(3)H]cyclopentyl-1,3-dipropylxanthine in the hippocampus, and their greater sensitivity to convulsant stimuli than that in TAG-1 (+/+) mice [14].

Anatomical context of Cntn2

  • Trigeminal ganglia were harvested from embryonic day 13.5 mouse embryos, and Bcl-2 and TAG-1 expression were measured by RT-PCR [15].
  • TAG-1 expression was also examined in the embryonic trigeminal and dorsal root ganglia by immunohistochemistry [15].
  • The adhesion molecule TAG-1 mediates the migration of cortical interneurons from the ganglionic eminence along the corticofugal fiber system [16].
  • 5. In contrast with its mRNA, the protein was intensely detected on the fasciculated axons in the floor plates, ventral root, and dorsal funiculus in the E10.5-11.5 spinal cord and colocalized with NCAM and L1 on the ventral root and dorsal funiculus and partly colocalized with TAG-1 on the commissural axons and dorsal funiculus [17].
  • In the E13.5-15.5 brain, RA175/TSLC1/SynCAM colocalized with NCAM and L1 on the developing thalamocortical fibers from the internal capsule (IC) and partly colocalized with TAG-1 on the cortical efferent axons in the intermediate zone (IZ) [17].

Associations of Cntn2 with chemical compounds

  • TAG-1-deficient mice have marked elevation of adenosine A1 receptors in the hippocampus [14].
  • Here, the expression of TAG-1/axonin-1 was investigated anatomically in the adult mouse brain by in situ hybridization using digoxigenin-labeled cRNA probes [18].
  • The arising effects were even stronger than those coming from the overall suppression of the F3 or, respectively, TAG-1 genes, thus supporting the hypothesis that the mechanisms underlying axonal glycoprotein regulated expression are themselves endowed with a key significance in neural development [19].
  • However, the effect of PS-341 on the growth of tumors in Tax transgenic mice revealed heterogeneity in drug responsiveness [3].
  • Three general classes of receptor systems were analyzed, the neuron-glial adhesion ligand astrotactin, the neural cell adhesion molecules of the IgG superfamily, N-CAM, L1 and TAG-1, and the beta 1 subunit of the integrin family [20].

Regulatory relationships of Cntn2

  • Netrin 1 promotes the exit of postmitotic migrating neurons from the embryonic lower rhombic lip and upregulates the expression of TAG-1 in these neurons [21].
  • In a complementary model, transgenic mice have been generated which express the F3 cDNA under control of a selected regulatory region from the TAG-1 gene [19].

Other interactions of Cntn2


Analytical, diagnostic and therapeutic context of Cntn2

  • Immunoprecipitation and cross-blocking with antiserum to TAG-1 suggested that OZ42 recognized the same molecule in the mouse cerebellum that has been described in embryonic rat and mouse spinal cord [25].
  • Indeed, several studies have suggested that upregulation of various cellular oncogenes and cytokines by Tax may explain the pathogenesis observed in HTLV-I-infected individuals, as well as several Tax-transgenic animal models [26].
  • These results demonstrate the activation of Tax-specific CD8+ T cells by vaccination and are supportive of a multivalent peptide vaccine approach against HTLV-1 infections [27].


  1. Growth-associated protein-43 is required for commissural axon guidance in the developing vertebrate nervous system. Shen, Y., Mani, S., Donovan, S.L., Schwob, J.E., Meiri, K.F. J. Neurosci. (2002) [Pubmed]
  2. Development of leukemia in mice transgenic for the tax gene of human T-cell leukemia virus type I. Grossman, W.J., Kimata, J.T., Wong, F.H., Zutter, M., Ley, T.J., Ratner, L. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  3. Effects of the proteasome inhibitor PS-341 on tumor growth in HTLV-1 Tax transgenic mice and Tax tumor transplants. Mitra-Kaushik, S., Harding, J.C., Hess, J.L., Ratner, L. Blood (2004) [Pubmed]
  4. Lethal cutaneous disease in transgenic mice conditionally expressing type I human T cell leukemia virus Tax. Kwon, H., Ogle, L., Benitez, B., Bohuslav, J., Montano, M., Felsher, D.W., Greene, W.C. J. Biol. Chem. (2005) [Pubmed]
  5. The region between amino acids 245 and 265 of the bovine leukemia virus (BLV) tax protein restricts transactivation not only via the BLV enhancer but also via other retrovirus enhancers. Tajima, S., Aida, Y. J. Virol. (2000) [Pubmed]
  6. The weaver gene encodes a nonautonomous signal for CNS neuronal differentiation. Gao, W.Q., Liu, X.L., Hatten, M.E. Cell (1992) [Pubmed]
  7. Juxtaparanodal clustering of Shaker-like K+ channels in myelinated axons depends on Caspr2 and TAG-1. Poliak, S., Salomon, D., Elhanany, H., Sabanay, H., Kiernan, B., Pevny, L., Stewart, C.L., Xu, X., Chiu, S.Y., Shrager, P., Furley, A.J., Peles, E. J. Cell Biol. (2003) [Pubmed]
  8. Neurite fasciculation mediated by complexes of axonin-1 and Ng cell adhesion molecule. Kunz, S., Spirig, M., Ginsburg, C., Buchstaller, A., Berger, P., Lanz, R., Rader, C., Vogt, L., Kunz, B., Sonderegger, P. J. Cell Biol. (1998) [Pubmed]
  9. Phorbol esters modulate the phosphorylation of human T-cell leukemia virus type I Tax. Fontes, J.D., Strawhecker, J.M., Bills, N.D., Lewis, R.E., Hinrichs, S.H. J. Virol. (1993) [Pubmed]
  10. Role of Emx2 in the development of the reciprocal connectivity between cortex and thalamus. López-Bendito, G., Chan, C.H., Mallamaci, A., Parnavelas, J., Molnár, Z. J. Comp. Neurol. (2002) [Pubmed]
  11. A combination of chain and neurophilic migration involving the adhesion molecule TAG-1 in the caudal medulla. Kyriakopoulou, K., de Diego, I., Wassef, M., Karagogeos, D. Development (2002) [Pubmed]
  12. Axonin-1/TAG-1 mediates cell-cell adhesion by a cis-assisted trans-interaction. Kunz, B., Lierheimer, R., Rader, C., Spirig, M., Ziegler, U., Sonderegger, P. J. Biol. Chem. (2002) [Pubmed]
  13. The adhesion molecule TAG-1 is required for proper migration of the superficial migratory stream in the medulla but not of cortical interneurons. Denaxa, M., Kyriakopoulou, K., Theodorakis, K., Trichas, G., Vidaki, M., Takeda, Y., Watanabe, K., Karagogeos, D. Dev. Biol. (2005) [Pubmed]
  14. TAG-1-deficient mice have marked elevation of adenosine A1 receptors in the hippocampus. Fukamauchi, F., Aihara, O., Wang, Y.J., Akasaka, K., Takeda, Y., Horie, M., Kawano, H., Sudo, K., Asano, M., Watanabe, K., Iwakura, Y. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  15. Unaltered expression of Bcl-2 and TAG-1/axonin-1 precedes sensory apoptosis in Brn3a knockout mice. Eng, S.R., Kozlov, S., Turner, E.E. Neuroreport (2003) [Pubmed]
  16. The adhesion molecule TAG-1 mediates the migration of cortical interneurons from the ganglionic eminence along the corticofugal fiber system. Denaxa, M., Chan, C.H., Schachner, M., Parnavelas, J.G., Karagogeos, D. Development (2001) [Pubmed]
  17. Distribution of RA175/TSLC1/SynCAM, a member of the immunoglobulin superfamily, in the developing nervous system. Fujita, E., Urase, K., Soyama, A., Kouroku, Y., Momoi, T. Brain Res. Dev. Brain Res. (2005) [Pubmed]
  18. Expression of the axon growth-related neural adhesion molecule TAG-1/axonin-1 in the adult mouse brain. Wolfer, D.P., Giger, R.J., Stagliar, M., Sonderegger, P., Lipp, H.P. Anat. Embryol. (1998) [Pubmed]
  19. Transgenic models for studying expression and function of axonal adhesive glycoproteins. De Benedictis, L., Bizzoca, A., Gennarini, G. Archives italiennes de biologie. (2005) [Pubmed]
  20. Astrotactin provides a receptor system for CNS neuronal migration. Fishell, G., Hatten, M.E. Development (1991) [Pubmed]
  21. Netrin 1 acts as an attractive or as a repulsive cue for distinct migrating neurons during the development of the cerebellar system. Alcántara, S., Ruiz, M., De Castro, F., Soriano, E., Sotelo, C. Development (2000) [Pubmed]
  22. Pax6 is required for the normal development of the forebrain axonal connections. Jones, L., López-Bendito, G., Gruss, P., Stoykova, A., Molnár, Z. Development (2002) [Pubmed]
  23. Overexpression of MATH1 disrupts the coordination of neural differentiation in cerebellum development. Helms, A.W., Gowan, K., Abney, A., Savage, T., Johnson, J.E. Mol. Cell. Neurosci. (2001) [Pubmed]
  24. Transgenic mice expressing F3/contactin from the transient axonal glycoprotein promoter undergo developmentally regulated deficits of the cerebellar function. Coluccia, A., Tattoli, M., Bizzoca, A., Arbia, S., Lorusso, L., De Benedictis, L., Buttiglione, M., Cuomo, V., Furley, A., Gennarini, G., Cagiano, R. Neuroscience (2004) [Pubmed]
  25. Transiently expressed, neural-specific molecule associated with premigratory granule cells in postnatal mouse cerebellum. Pickford, L.B., Mayer, D.N., Bolin, L.M., Rouse, R.V. J. Neurocytol. (1989) [Pubmed]
  26. Cytokine expression and tumorigenicity of large granular lymphocytic leukemia cells from mice transgenic for the tax gene of human T-cell leukemia virus type I. Grossman, W.J., Ratner, L. Blood (1997) [Pubmed]
  27. Protective efficacy of multiepitope human leukocyte antigen-A*0201 restricted cytotoxic T-lymphocyte peptide construct against challenge with human T-cell lymphotropic virus type 1 Tax recombinant vaccinia virus. Sundaram, R., Lynch, M.P., Rawale, S., Dakappagari, N., Young, D., Walker, C.M., Lemonnier, F., Jacobson, S., Kaumaya, P.T. J. Acquir. Immune Defic. Syndr. (2004) [Pubmed]
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