Structural requirement of TAG-1 for retinal ganglion cell axons and myelin in the mouse optic nerve.
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.
Chatzopoulou
Elli
E
Institut National de la Santé et de la Recherche Médicale, Unité 711, Université Pierre et Marie Curie, Faculté de Médecine, Hôpital de la Salpêtrière, Institut Fédératif de Recherche 70, F-75013 Paris, France.
Miguez
Andrés
A
Savvaki
Maria
M
Levasseur
Grégoire
G
Muzerelle
Aude
A
Muriel
Marie-Paule
MP
Goureau
Olivier
O
Watanabe
Kazutada
K
Goutebroze
Laurence
L
Gaspar
Patricia
P
Zalc
Bernard
B
Karagogeos
Domna
D
Thomas
Jean-Léon
JL
D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000502:physiology* / Q000648:ultrastructure; D015816:Cell Adhesion Molecules, Neuronal / Q000172:deficiency / Q000502:physiology*; D002478:Cells, Cultured; D058969:Contactin 2; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D039841:Leukocyte L1 Antigen Complex / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism; D009900:Optic Nerve / Q000378:metabolism* / Q000648:ultrastructure; D012160:Retina / Q000166:cytology*; D012165:Retinal Ganglion Cells / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D050819:Transcription Factor Brn-3A / Q000235:genetics / Q000378:metabolism
D015816:Cell Adhesion Molecules, Neuronal; C548675:Cntn2 protein, mouse; D058969:Contactin 2; D039841:Leukocyte L1 Antigen Complex; D009419:Nerve Tissue Proteins; C494189:Pou4f1 protein, mouse; D050819:Transcription Factor Brn-3A