We are interested in neuronal development and axoglial interactions during myelination.
Neuronal development: We study the genetic, molecular and cellular bases of neurogenesis, neuronal migration and axon guidance. We focus on:
1) the function of the immunoglobulin superfamily protein TAG-1/Contactin-2 and its partners in axon guidance and neuronal migration in mice
2) the role of small GTPases in cortical interneuron development
Axoglial interactions during myelination: Myelinated fibers are organized into distinct functional domains as a consequence of their interactions with glial cells. How is the molecular organization and functional architecture of myelinated fibers achieved? How is it perturbed in de-myelinating diseases, such as multiple sclerosis? We study how TAG-1 and its partners, expressed at specific sites of myelin/axon interactions, contribute to these interactions and how deregulation of these proteins' function is involved in de-myelinating diseases.
Experimental approaches: We use a combination of genetic, molecular, cellular and functional approaches: transgenic animal models, ex-vivo transplantation systems, proteomics analysis, real time-PCR, imaging, primary cultures, electrophysiological and behavioural analysis.
Zoupi L, Savvaki M, Kalemaki K, Kalafatakis I, Sidiropoulou K, Karagogeos D. (2018) The function of contactin-2/TAG-1 in oligodendrocytes in health and demyelinating pathology. Glia 66:576-591.
Bastakis GG, Savvaki M, Stamatakis A, Vidaki M, Karagogeos D. (2015) Tag1 deficiency results in olfactory dysfunction through impaired migration of mitral cells. Development 142:4318-28.
Savvaki M, Theodorakis K, Zoupi L, Stamatakis A, Tivodar S, Kyriacou K, Stylianopoulou F, Karagogeos D. (2010) The Expression of TAG-1 in Glial Cells is Sufficient for the Formation of the Juxtaparanodal Complex and the Phenotypic Rescue of Tag-1 Homozygous Mutants in the CNS. J. Neurosci 30:13943-54.
Ma QH, Futagawa T, Yang WL, Jiang XD, Zeng L, Takeda Y, Xu RX, Bagnard D, Schachner M, Furley AJ, Karagogeos D, Watanabe K, Dawe GS, Xiao ZC. (2008) A TAG1-APP signalling pathway through Fe65 negatively modulates neurogenesis. Nat Cell Biol. 10:283-94.
Traka M, Goutebroze L, Denisenko N, Bessa M, Nifli F, Havaki S, Iwakura Y, Fukamauchi F, Watanabe K, Girault JA. Karagogeos D. (2003) TAG-1 associates with Caspr-2 and is essential for the molecular organization of juxtaparanodal regions of myelinated fibers. J Cell Biol. 162:1161-1172.
Recent Publications (since 2000)
Kounoupa Z, Tivodar S, Theodorakis K, Kyriakis D, Denaxa M, Karagogeos D. (2023) Rac1, Rac3 GTPases and TPC2 are required for axonal outgrowth and migration of cortical interneurons. J Cell Sci. 2023 Feb 6:jcs.260373. doi: 10.1242/jcs.260373. Online ahead of print.
Ktena N, Kaplanis SI, Kolotuev I, Georgilis A, Kallergi E, Stavroulaki V, Nikoletopoulou V, Savvaki M, Karagogeos D. (2022) Autophagic degradation of CNS myelin maintains axon integrity. Cell Stress. 2022 Nov 21;6(12):93-107. doi: 10.15698/cst2022.12.274.
Kalemaki K, Velli A, Christodoulou O, Denaxa M, Karagogeos D, Sidiropoulou K. (2022) The Developmental Changes in Intrinsic and Synaptic Properties of Prefrontal Neurons Enhance Local Network Activity from the Second to the Third Postnatal Weeks in Mice. Cereb Cortex. 2022 Aug 22;32(17):3633-3650. doi: 10.1093/cercor/bhab438.
Kalafatakis I, Karagogeos D. (2021) Oligodendrocytes and Microglia: Key Players in Myelin Development, Damage and Repair. Biomolecules. 2021 Jul 20;11(7):1058. doi: 10.3390/biom11071058.
Kalafatakis I, Patellis A, Charalampopoulos I, Gravanis A, Karagogeos D. (2021) The beneficial role of the synthetic microneurotrophin BNN20 in a focal demyelination model. J Neurosci Res. 2021 May;99(5):1474-1495. doi: 10.1002/jnr.24809.
Savvaki M, Kafetzis G, Kaplanis SI, Ktena N, Theodorakis K, Karagogeos D. (2021) Neuronal, but not glial Contactin 2, negatively regulates axon regeneration in the injured adult optic nerve. Eur J Neurosci. 2021 Mar;53(6):1705-1721. doi: 10.1111/ejn.15121.
Kalafatakis I, Savvaki M, Velona T, Karagogeos D. (2021) Implication of Contactins in Demyelinating Pathologies. Life (Basel). 2021 Jan 13;11(1):51. doi: 10.3390/life11010051.
Kalafatakis I, Kalafatakis K, Tsimpolis A, Giannakeas N, Tsipouras M, Tzallas A, Karagogeos D. (2020) Using the Allen gene expression atlas of the adult mouse brain to gain further insight into the physiological significance of TAG-1/Contactin-2. Brain Struct Funct. 2020 Jun 29. doi: 10.1007/s00429-020-02108-4.
Theodosiou T, Papanikolaou N, Savvaki M, Bonetto G, Maxouri S, Fakoureli E, Eliopoulos AG, Tavernarakis N, Amoutzias GD, Pavlopoulos GA, Aivaliotis M, Nikoletopoulou V, Tzamarias D, Karagogeos D, Iliopoulos I. (2020) UniProt-Related Documents (UniReD): assisting wet lab biologists in their quest on finding novel counterparts in a protein network. NAR Genomics and Bioinformatics, 2020 1–13. doi: 10.1093/nargab/lqaa005.
Kastriti ME, Stratigi A, Mariatos D, Theodosiou M, Savvaki M, Kavkova M, Theodorakis K, Vidaki M, Zikmund T, Kaiser J, Adameyko I, Karagogeos D. (2019) Ablation of CNTN2+ Pyramidal Neurons During Development Results in Defects in Neocortical Size and Axonal Tract Formation. Front Cell Neurosci. 2019 Nov 1;13:454. doi: 10.3389/fncel.2019.00454.
Saint-Martin M, Pieters A, Déchelotte B, Malleval C, Pinatel D, Pascual O, Karagogeos D, Honnorat J, Pellier-Monnin V, Noraz N. (2019) Impact of anti-CASPR2 autoantibodies from patients with autoimmune encephalitis on CASPR2/TAG-1 interaction and Kv1 expression. J Autoimmun. 2019 Sep;103:102284. doi: 10.1016/j.jaut.2019.05.012.
Bastakis GG, Ktena N, Karagogeos D, Savvaki M. (2019) Models and treatments for traumatic optic neuropathy and demyelinating optic neuritis. Dev Neurobiol. 2019 Jul 11. doi: 10.1002/dneu.22710. [Epub ahead of print] Review.
Kalemaki K, Konstantoudaki X, Tivodar S, Sidiropoulou K, Karagogeos D. (2018) Mice With Decreased Number of Interneurons Exhibit Aberrant Spontaneous and Oscillatory Activity in the Cortex. Front Neural Circuits. 2018 Oct 31;12:96. doi: 10.3389/fncir.2018.00096. eCollection 2018.
Zoupi L, Savvaki M, Kalemaki K, Kalafatakis I, Sidiropoulou K, Karagogeos D. (2018) The function of contactin-2/TAG-1 in oligodendrocytes in health and demyelinating pathology. Glia. 66(3):576-591.
Bonetto G, Charalampopoulos I, Gravanis A, Karagogeos D. (2017) The novel synthetic microneurotrophin BNN27 protects mature oligodendrocytes against cuprizone-induced death, through the NGF receptor TrkA. Glia. 65(8):1376-1394.
Pinatel D, Hivert B, Saint-Martin M, Noraz N, Savvaki M, Karagogeos D, Faivre-Sarrailh C. (2017) The Kv1-associated molecules TAG-1 and Caspr2 are selectively targeted to axon initial segment in hippocampal neurons. J Cell Sci. 2017 May 22. pii: jcs.202267. doi: 10.1242/jcs.202267
Bastakis GG, Savvaki M, Stamatakis A, Vidaki M, Karagogeos D. (2015) Tag1 deficiency results in olfactory dysfunction through impaired migration of mitral cells. Development. 142(24):4318-28.
Pinatel D, Hivert B, Boucraut J, Saint-Martin M, Rogemond V, Zoupi L, Karagogeos D, Honnorat J, Faivre-Sarrailh C. (2015) Inhibitory axons are targeted in hippocampal cell culture by anti-Caspr2 autoantibodies associated with limbic encephalitis. Front Cell Neurosci. 2015 Jul 9;9:265
Tsikala G, Karagogeos D, Strigini M. (2014) Btk-dependent epithelial cell rearrangements contribute to the invagination of nearby tubular structures in the posterior spiracles of Drosophila.Dev Biol 396(1): 42-56.
Schmidt ER, Brignani S, Adolfs Y, Lemstra S, Demmers J, Vidaki M, Donahoo AL, Lilleväli K, Vasar E, Richards LJ, Karagogeos D, Kolk SM, Pasterkamp RJ. (2014) Subdomain-mediated axon-axon signaling and chemoattraction cooperate to regulate afferent innervation of the lateral habenula. Neuron. 2014 83(2):372-87
Tivodar S, Kalemaki K, Kounoupa Z, Vidaki M, Theodorakis K, Denaxa M, Kessaris N, de Curtis I, Pachnis V, Karagogeos D. (2014) Rac-GTPases Regulate Microtubule Stability and Axon Growth of Cortical GABAergic Interneurons. Cereb Cortex. 2014 Apr 1. [Epub ahead of print]
Zoupi L, Markoullis K, Kleopa KA, Karagogeos D. (2013) Alterations of juxtaparanodal domains in two rodent models of CNS demyelination. Glia. 61(8):1236-49
Katidou M, Tavernarakis N, Karagogeos D. (2013) The contactin RIG-6 mediates neuronal and non-neuronal cell migration in Caenorhabditis elegans. Dev Biol. 373(1):184-95
Vidaki M, Tivodar, S., Doulgeraki K, Tybulewicz, V., Kessaris N, Pachnis, V. and Karagogeos D. (2012) Rac1-Dependent Cell Cycle Exit of MGE Precursors and GABAergic Interneuron Migration to the Cortex. Cerebral Cortex 22(3):680-92
Zoupi L, Savvaki M, Karagogeos D. (2011) Axons and myelinating glia: An intimate contact. IUBMB Life. 63(9):730-5
Wang, W., Karagogeos, D . and Kilpatrick, DL. (2011) The effects of Tag-1 on the maturation of mouse cerebellar granule neurons. Cell Mol Neurobiol. 31(3):351-6
Savvaki, M, Theodorakis, K., Zoupi, L., Stamatakis, A., Tivodar, S., Kyriacou, K., Stylianopoulou, F., and Karagogeos, D. (2010) The Expression of TAG-1 in Glial Cells is Sufficient for the Formation of the Juxtaparanodal Complex and the Phenotypic Rescue of Tag-1 Homozygous Mutants in the CNS. J. Neurosci., 30(42):13943-54
Sakurai K, Toyoshima M, Ueda H, Matsubara K, Takeda Y, Karagogeos D, Shimoda Y, Watanabe K. (2009) Contribution of the neural cell recognition molecule NB-3 to synapse formation between parallel fibers and Purkinje cells in mouse. Dev Neurobiol. 69(12):811-2
Derfuss T., Parikh K., Velhin S., Braun M., Mathey E., Krumbholz M., Kumpfel T., Moldenhauer A., Kunz B., Pollmann W, Tiefenthaller C, Bauer J, Lassmann H, Wekerle , H., Karagogeos D , Hohlfeld R., Linington C., Meinl E. (2009) Contactin-2/Tag-1 directed autoimmunity is identified in multiple sclerosis patients and mediates gray matter pathology in animals PNAS USA 106(20):8302-7
Lieberoth A, Splittstoesser F, Katagihallimath N, Jakovcevski I, Loers G, Ranscht B, Karagogeos D , Schachner M, Kleene R . (2009) Lewis (x) and alpha 2,3 sialyl glycans and their receptors TAG-1, Contactin and L1 mediate CD24-dependent neurite outgrowth J. Neurosci. 29(20):6677-90
Katidou M, Vidaki M, Strigini M, Karagogeos D. (2008) The immunoglobulin superfamily of neuronal cell adhesion molecules: lessons from animal models and correlation with human disease Biotechnol J . 3(12):1564-80
Savvaki M, Panagiotaropoulos T, Stamatakis A, Sargiannidou I, Karatzioula P, Watanabe K, Stylianopoulou F, Karagogeos D, Kleopa KA. (2008) Impairment of learning and memory in TAG-1 deficient mice associated with shorter CNS internodes and disrupted juxtaparanodes. Mol Cell Neurosci . 39(3):478-90
Chatzopoulou E, Miguez A, Savvaki M, Levasseur G, Muzerelle A, Muriel MP, Goureau O, Watanabe K, Goutebroze L, Gaspar P, Zalc B, Karagogeos D, Thomas JL. (2008) Structural requirement of TAG-1 for retinal ganglion cell axons and myelin in the mouse optic nerve. J Neurosci. 23;28(30):7624-36
Ma QH, Futagawa T, Yang WL, Jiang XD, Zeng L, Takeda Y, Xu RX, Bagnard D, Schachner M, Furley AJ, Karagogeos D, Watanabe K, Dawe GS, Xiao ZC. (2008) A TAG1-APP signalling pathway through Fe65 negatively modulates neurogenesis. Nat Cell Biol. 10(3):283-94. Erratum in: Nat Cell Biol. 2008, 10(4):497
McLaughlin D, Vidaki M, and Karagogeos D. (2008) Localization of CRMP5 mRNA by in situ hybridisation during development of the mouse forebrain. Neurosci Lett. 432(2):117-20
Tzimourakas, A., Giasemi, S., Mouratidou, M., and Karagogeos, D. (2007) Structure-function analysis of protein complexes involved in the molecular architecture of juxtaparanodal regions of myelinated fibers Biotechnol. J 2(5):577-83
Strigini, M., Cantera, R., Morin, X., Bastiani, M., Bate, M., and Karagogeos, D. (2006) The IgLON protein Lachesin, is required for the blood-brain barrier in Drosophila Mol Cell Neurosci. 32(1-2):91-101.
McLaughlin, D., Vidaki, M., Renieri, E. and Karagogeos, D. (2006) Expression pattern of the maternally imprinted gene Gt12 in the forebrain during embryonic development and adulthood Mech Dev GEP 6(4):394-9
Denaxa, M., Kyriakopoulou, K., Theodorakis, K., Trichas, G., Vidaki, M., Takeda, Y., Watanabe, K., and Karagogeos, D. (2005) The adhesion molecule TAG-1 is required for proper migration of the superficial migratory stream in the medulla but not of cortical interneurons Dev. Biol. 288(1):87-99
Ekonomou,A., Kazanis,I., Malas,S., Wood,H., Alifragkis, P., Denaxa, M., Karagogeos, D., Constanti, A., Lovell-Badge, R., Episkopou, V. (2005) Neuronal migration and ventral subtype identity in the telencephalon depend on SOX1 PLoS Biol. 3(6):e186
Soares*, S., Traka*, M., vonBoxberg, Y., Karagogeos, D. and Nothias, F. (2005) Neuronal and glial expression of the adhesion molecule TAG-1 is regulated after peripheral nerve lesion or central neurodegeneration of adult nervous system. Eur. J. Neurosci. 21(5): 1169-1180
* Equal contribution
Llimargas, M. *, Strigini, M. *, Katidou, M., Karagogeos, D. and Casanova, J. (2004) Lachesin is a component of a septate junction based mechanism that controls tube size and epithelial integrity in the Drosophila tracheal system Development 131(1):181-90
* Equal contribution
Denaxa*, M., Pavlou*, O., Tsiotra, P., Papadopoulos, G.C., Liapaki, K., Theodorakis, K., Karagogeos+, D., and Papamatheakis+, J. (2003) The upstream regulatory region of the human homologue of the neuronal cell adhesion molecule TAG-1 gene contains elements driving neural specific expression in vivo Molecular Brain Research 118:91-101
* Equal contribution, + Equal senior contribution
Traka, M. *, Goutebroze, L. *, Denisenko, N., Bessa, M., Nifli, F., Havaki, S., Iwakura, Y., Fukamauchi, F., Watanabe, K., Girault, J.A. and Karagogeos, D. (2003) TAG-1 associates with Caspr-2 and is essential for the molecular organization of juxtaparanodal regions of myelinated fibers J Cell Biol 162 (6): 1161-1172
* Equal contribution
Karagogeos, D. (2003) Neural GPI-anchored cell adhesion molecules Invited Review Front. Biosci. 8, S13011-1320, Sept 1.
[PubMed#:pending]
Loberto, N., Prioni, S., Prinetti, A., Ottico, E., Chigorno, V., Karagogeos, D. and Sonnino, S. (2003) The adhesion protein TAG-1 has a ganglioside environment in the sphingolipid-enriched membrane domains of neuronal cells in culture. J. Neurochem. 85: 224-233
Theodorakis, K., Kyriakopoulou, K., Wassef, M., and Karagogeos, D. (2002) Novel sites of expression of the bHLH gene NSCL1 in the developing nervous system. Mech. Dev. 119S: 103-S106
Pavlou, O., Theodorakis, C., Falk, J., Kutsche, M., Schachner, M., Faivre-Sarrailh, C., and Karagogeos, D. (2002) Analysis of Interactions of the adhesion molecule TAG-1 and Its domains with other Immunoglobulin superfamily members Mol. Cell. Neurosci. 20: 367-381
Traka, M. Dupree, J.L., Popko, B. and Karagogeos, D. (2002) The neuronal adhesion protein TAG-1 is expressed by Schwann cells and oligodendrocytes and is localized to the region of the node of Ranvier in myelinated fibers. J. Neurosci. 22(8):3016-3024
De Diego, I., Kyriakopoulou, K., Karagogeos, D. and Wassef, M. (2002) Multiple influences on the migration of precerebellar neurons in the caudal medulla Development 129: 297-306
Kyriakopoulou, K., DeDiego, I., Wassef, M. and Karagogeos, D. (2002) A combination of chain and neurophilic migration involving the adhesion molecule TAG-1 in the caudal medulla Development 129: 287-296
Denaxa, M., Chan, C-H., Schachner, M., Parnavelas, J.G. and Karagogeos, D. (2001) The adhesion molecule TAG-1 mediates the migration of cortical interneurons along the corticofugal fiber system Development 128: 4635-4644
Prinetti, A., Prioni, S., Chigorno, V., Karagogeos, D., Tettamanti, G. and Sonnino, S. (2001) Immunoseparation of sphingolipid-enriched membrane domains enriched in Src family protein tyrosine kinases and in neuronal adhesion molecule TAG-1 by anti-GD3 ganglioside monoclonal antibody J. Neurochem. 78 (5):1162-7
Stamataki, D., Kastrinaki, M-C., Mankoo, B.S., Pachnis, V. and Karagogeos, D. (2001) Homeodomain proteins Mox1 and Mox2 associate with Pax1 and Pax3 transcription factors. FEBS Lett., 499(3):274-8. Medline Abstract
Rallis, C., Stamataki, D., Pontikakis, S., Mankoo, B.S., and Karagogeos, D. (2001) Isolation of the avian homologue of the homeobox gene Mox2 and analysis of its expression pattern in developing somites and limbs. Mech. Dev. 104:121-124