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The Journal of Neuroscience, July 23, 2008, 28(30):7624-7636; doi:10.1523/JNEUROSCI.1103-08.2008

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Cellular/Molecular
Structural Requirement of TAG-1 for Retinal Ganglion Cell Axons and Myelin in the Mouse Optic Nerve

Elli Chatzopoulou,^1,3 * Andrés Miguez,^1,3 * Maria Savvaki,⁶ Grégoire Levasseur,^3,4 Aude Muzerelle,^3,4 Marie-Paule Muriel,^2,3 Olivier Goureau,^3,5 Kazutada Watanabe,⁷ Laurence Goutebroze,^3,4 Patricia Gaspar,^3,4 Bernard Zalc,^1,3 Domna Karagogeos,⁶ and Jean-Léon Thomas^1,3

¹Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 711, ²INSERM, Unité 679, ³Université Pierre et Marie Curie, Faculté de Médecine, Hôpital de la Salpêtrière, Institut Fédératif de Recherche 70, F-75013 Paris, France, ⁴INSERM, Unité 839, Institut du Fer à Moulin, F-75005 Paris, France, ⁵INSERM, Unité Mixte de Recherche en Santé 592, Hôpital Saint-Antoine, F-75012 Paris, France, ⁶University of Crete Medical School and Institute of Molecular Biology and Biotechnology, 711 10 Heraklion, Greece, and ⁷Department of Bioengineering, Nagaoka University of Technology, Kamitomioka, Nagaoka, Niigata 940-2188, Japan

Correspondence should be addressed to Jean-Léon Thomas, Unité Mixte de Recherche, Institut National de la Santé et de la Recherche Médicale, Unité 711, Université Pierre et Marie Curie, Hôpital de la Salpêtrière, 47 boulevard de l'Hôpital, F-75651 Paris Cedex 13, France. Email: jean-leon.thomas{at}upmc.fr

White matter axons organize into fascicles that grow over long distances and traverse very diverse environments. The molecular mechanisms preserving this structure of white matter axonal tracts are not well known. Here, we used the optic nerve as a model and investigated the role of TAG-1, a cell adhesion molecule expressed by retinal axons. TAG-1 was first expressed in the embryonic retinal ganglion cells (RGCs) and later in the postnatal myelin-forming cells in the optic nerve. We describe the consequences of genetic loss of Tag-1 on the developing and adult retinogeniculate tract. Tag-1-null embryos display anomalies in the caliber of RGC axons, associated with an abnormal organization of the astroglial network in the optic nerve. The contralateral projections in the lateral geniculate nucleus are expanded postnatally. In the adult, Tag-1-null mice show a loss of RGC axons, with persistent abnormalities of axonal caliber and additional cytoskeleton and myelination defects. Therefore, TAG-1 is an essential regulator of the structure of RGC axons and their surrounding glial cells in the optic nerve.

Key words: CAM; retinal ganglion cell; optic nerve; axon; myelin; astrocyte

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Received March 13, 2008; revised June 6, 2008; accepted June 9, 2008.

Correspondence should be addressed to Jean-Léon Thomas, Unité Mixte de Recherche, Institut National de la Santé et de la Recherche Médicale, Unité 711, Université Pierre et Marie Curie, Hôpital de la Salpêtrière, 47 boulevard de l'Hôpital, F-75651 Paris Cedex 13, France. Email: jean-leon.thomas{at}upmc.fr

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