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Gene Review

Dcx  -  doublecortin

Mus musculus

Synonyms: Dbct, Dcn, Doublin, Lis-X, Lissencephalin-X, ...
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Disease relevance of Dcx


High impact information on Dcx

  • Doublecortin maintains bipolar shape and nuclear translocation during migration in the adult forebrain [5].
  • A second locus, doublecortin-like kinase (Dclk), encodes a protein with similar "doublecortin domains" and microtubule stabilization properties that may compensate for Dcx [6].
  • Dcx and Dclk may directly or indirectly regulate microtubule-based vesicle transport, a process critical to both neuronal migration and axon outgrowth [6].
  • Dcx/Dclk-deficient dissociated neurons show abnormal axon outgrowth and dendritic structure, with defects in axonal transport of synaptic vesicle proteins [6].
  • Doublecortin-like kinase controls neurogenesis by regulating mitotic spindles and M phase progression [7].

Chemical compound and disease context of Dcx


Biological context of Dcx


Anatomical context of Dcx


Associations of Dcx with chemical compounds

  • Early after BrdU, CR colocalized with immature neuronal marker doublecortin; and later with persisting neuronal marker NeuN [15].
  • Ipsilateral GCD progressively developed after KA injection and was paralleled by a gradual decrease in the expression of doublecortin, a marker of newly generated granule cells, in the dentate subgranular layer [16].
  • In vitro assays (using biochemical methods, DIC microscopy and electron microscopy) demonstrate that Doublecortin binds microtubules directly, stabilizes them and causes bundling [17].
  • Therefore, SGZ progenitor cells committed to a neuronal phenotype before KA treatment complete their differentiation despite the rapid down-regulation of doublecortin and PSA-NCAM [18].
  • In addition, blocking endothelial nitric oxide synthase activity (via a daily injection of 20 mg/kg L-nitroimidazole ornithine) during exercise reduced the number of cells within the dentate gyrus that were immunoreactive for Ki-67 protein and doublecortin [19].

Regulatory relationships of Dcx

  • The isolated kinase domain retains catalytic activity and is structurally similar to CPG16, a second product of the DCLK gene expressed in the adult brain that lacks the doublecortin domain [20].

Other interactions of Dcx


Analytical, diagnostic and therapeutic context of Dcx


  1. Mutational and expression analysis of the reelin pathway components CDK5 and doublecortin in gangliogliomas. Becker, A.J., Klein, H., Baden, T., Aigner, L., Normann, S., Elger, C.E., Schramm, J., Wiestler, O.D., Blümcke, I. Acta Neuropathol. (2002) [Pubmed]
  2. Ectopic doublecortin gene expression suppresses the malignant phenotype in glioblastoma cells. Santra, M., Zhang, X., Santra, S., Jiang, F., Chopp, M. Cancer Res. (2006) [Pubmed]
  3. Neuronal nitric oxide synthase and ischemia-induced neurogenesis. Sun, Y., Jin, K., Childs, J.T., Xie, L., Mao, X.O., Greenberg, D.A. J. Cereb. Blood Flow Metab. (2005) [Pubmed]
  4. Doublecortin is preferentially expressed in invasive human brain tumors. Daou, M.C., Smith, T.W., Litofsky, N.S., Hsieh, C.C., Ross, A.H. Acta Neuropathol. (2005) [Pubmed]
  5. Doublecortin maintains bipolar shape and nuclear translocation during migration in the adult forebrain. Koizumi, H., Higginbotham, H., Poon, T., Tanaka, T., Brinkman, B.C., Gleeson, J.G. Nat. Neurosci. (2006) [Pubmed]
  6. Genetic interactions between doublecortin and doublecortin-like kinase in neuronal migration and axon outgrowth. Deuel, T.A., Liu, J.S., Corbo, J.C., Yoo, S.Y., Rorke-Adams, L.B., Walsh, C.A. Neuron (2006) [Pubmed]
  7. Doublecortin-like kinase controls neurogenesis by regulating mitotic spindles and M phase progression. Shu, T., Tseng, H.C., Sapir, T., Stern, P., Zhou, Y., Sanada, K., Fischer, A., Coquelle, F.M., Reiner, O., Tsai, L.H. Neuron (2006) [Pubmed]
  8. Ectopic expression of doublecortin protects adult rat progenitor cells and human glioma cells from severe oxygen and glucose deprivation. Santra, M., Liu, X.S., Santra, S., Zhang, J., Zhang, R.L., Zhang, Z.G., Chopp, M. Neuroscience (2006) [Pubmed]
  9. Cdk5 phosphorylation of doublecortin ser297 regulates its effect on neuronal migration. Tanaka, T., Serneo, F.F., Tseng, H.C., Kulkarni, A.B., Tsai, L.H., Gleeson, J.G. Neuron (2004) [Pubmed]
  10. Identification of neurabin II as a novel doublecortin interacting protein. Tsukada, M., Prokscha, A., Oldekamp, J., Eichele, G. Mech. Dev. (2003) [Pubmed]
  11. Doublecortin association with actin filaments is regulated by neurabin II. Tsukada, M., Prokscha, A., Ungewickell, E., Eichele, G. J. Biol. Chem. (2005) [Pubmed]
  12. Doublecortin interacts with mu subunits of clathrin adaptor complexes in the developing nervous system. Friocourt, G., Chafey, P., Billuart, P., Koulakoff, A., Vinet, M.C., Schaar, B.T., McConnell, S.K., Francis, F., Chelly, J. Mol. Cell. Neurosci. (2001) [Pubmed]
  13. KIAA0369, doublecortin-like kinase, is expressed during brain development. Burgess, H.A., Martinez, S., Reiner, O. J. Neurosci. Res. (1999) [Pubmed]
  14. Cloning and developmental expression of the murine homolog of doublecortin. Matsuo, N., Kawamoto, S., Matsubara, K., Okubo, K. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  15. Transient calretinin expression defines early postmitotic step of neuronal differentiation in adult hippocampal neurogenesis of mice. Brandt, M.D., Jessberger, S., Steiner, B., Kronenberg, G., Reuter, K., Bick-Sander, A., von der Behrens, W., Kempermann, G. Mol. Cell. Neurosci. (2003) [Pubmed]
  16. Reelin deficiency and displacement of mature neurons, but not neurogenesis, underlie the formation of granule cell dispersion in the epileptic hippocampus. Heinrich, C., Nitta, N., Flubacher, A., Müller, M., Fahrner, A., Kirsch, M., Freiman, T., Suzuki, F., Depaulis, A., Frotscher, M., Haas, C.A. J. Neurosci. (2006) [Pubmed]
  17. Doublecortin, a stabilizer of microtubules. Horesh, D., Sapir, T., Francis, F., Wolf, S.G., Caspi, M., Elbaum, M., Chelly, J., Reiner, O. Hum. Mol. Genet. (1999) [Pubmed]
  18. Impairment of dentate gyrus neuronal progenitor cell differentiation in a mouse model of temporal lobe epilepsy. Ledergerber, D., Fritschy, J.M., Kralic, J.E. Exp. Neurol. (2006) [Pubmed]
  19. L-nitroimidazole ornithine limits exercise-induced increases in cell proliferation in the hippocampus of adult mice. Moon, M., Huh, Y., Park, C. Neuroreport (2006) [Pubmed]
  20. Cleavage of doublecortin-like kinase by calpain releases an active kinase fragment from a microtubule anchorage domain. Burgess, H.A., Reiner, O. J. Biol. Chem. (2001) [Pubmed]
  21. Multisite phosphorylation of doublecortin by cyclin-dependent kinase 5. Graham, M.E., Ruma-Haynes, P., Capes-Davis, A.G., Dunn, J.M., Tan, T.C., Valova, V.A., Robinson, P.J., Jeffrey, P.L. Biochem. J. (2004) [Pubmed]
  22. 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]
  23. Doublecortin is a developmentally regulated, microtubule-associated protein expressed in migrating and differentiating neurons. Francis, F., Koulakoff, A., Boucher, D., Chafey, P., Schaar, B., Vinet, M.C., Friocourt, G., McDonnell, N., Reiner, O., Kahn, A., McConnell, S.K., Berwald-Netter, Y., Denoulet, P., Chelly, J. Neuron (1999) [Pubmed]
  24. Heterotopia formation in rat but not mouse neocortex after RNA interference knockdown of DCX. Ramos, R.L., Bai, J., LoTurco, J.J. Cereb. Cortex (2006) [Pubmed]
  25. Magnetic resonance imaging and histological studies of corpus callosal and hippocampal abnormalities linked to doublecortin deficiency. Kappeler, C., Dhenain, M., Phan Dinh Tuy, F., Saillour, Y., Marty, S., Fallet-Bianco, C., Souville, I., Souil, E., Pinard, J.M., Meyer, G., Encha-Razavi, F., Volk, A., Beldjord, C., Chelly, J., Francis, F. J. Comp. Neurol. (2007) [Pubmed]
  26. Cerebral neurogenesis is induced by intranasal administration of growth factors. Jin, K., Xie, L., Childs, J., Sun, Y., Mao, X.O., Logvinova, A., Greenberg, D.A. Ann. Neurol. (2003) [Pubmed]
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