Inhibition of axon growth by oligodendrocyte precursor cells.
The glial scar that forms at the site of injury is thought to be a biochemical and physical barrier to successful regeneration, although the molecules responsible for this barrier function are not well understood. Glia scars contain large numbers of oligodendrocyte precursor cells (OPCs) and these cells can produce several different growth-inhibitory chondroitin sulfate proteoglycans (CSPGs), including NG2, neurocan, and phosphacan. Here, we used membrane-based assays to show that the surface of OPCs is both nonpermissive and inhibitory for neurite outgrowth. Inhibition of growth by OPC is reversed by treatment with antibodies against the NG2 CSPG and the expression of NG2 is sufficient to change a growth-permissive cell surface to a nonpermissive surface. These result suggest that the OPCs that accumulate rapidly at sites of CNS injury can contribute to the creation of an environment that inhibits nerve regeneration and that NG2 is a necessary feature of that environment.
Chen
Zhi Jiang
ZJ
Department of Neurobiology and Behavior, SUNY at Stony Brook, New York 11794, USA.
Ughrin
Yvonne
Y
Levine
Joel M
JM
D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000494:pharmacology; D000941:Antigens / Q000378:metabolism; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D030161:Avian Proteins; D051926:Basigin; D001681:Biological Assay; D001798:Blood Proteins; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002450:Cell Communication / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D002525:Cerebellar Cortex / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism; D020439:Growth Cones / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000378:metabolism; D009416:Nerve Regeneration / Q000502:physiology; D009433:Neural Inhibition / Q000502:physiology*; D016501:Neurites / Q000378:metabolism / Q000648:ultrastructure; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D018874:Spheroids, Cellular / Q000166:cytology / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D000099216:Chondroitin Sulfate Proteoglycan 4
D000906:Antibodies; D000941:Antigens; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D030161:Avian Proteins; D051926:Basigin; D001798:Blood Proteins; D015815:Cell Adhesion Molecules; D005904:Glial Fibrillary Acidic Protein; D006025:Glycosaminoglycans; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D011956:Receptors, Cell Surface; D000099216:Chondroitin Sulfate Proteoglycan 4; C497886:BSG protein, human; C102624:Bsg protein, Gallus gallus; C079432:Bsg protein, rat