Transient expression of neurofascin by oligodendrocytes at the onset of myelinogenesis: implications for mechanisms of axon-glial interaction.
Cell adhesion molecules (CAMs) must play a crucial role in both the initiation and signalling of axon-glial contact. However, the proteins that permit myelinating oligodendrocytes to recognize the axons that they ensheath in the developing CNS are unknown. By a subtractive cDNA library strategy, we have identified neurofascin as a powerful candidate for such a molecule. Neurofascin is strongly but transiently up-regulated in oligodendrocytes at the onset of myelinogenesis. Once oligodendrocytes have engaged their target axons the protein plays no further part, since the expression of the gene declines precipitously, in contrast to that of the major myelin component proteolipid protein, which remains elevated. After the initial surge of neurofascin expression in oligodendrocytes, there is a shift to a predominantly neuronal localization that persists into adulthood. Hence neurofascin in oligodendrocytes is unlikely to serve a function in the stabilization of the multilamellar sheath around the axon. The major neurofascin isoform of oligodendrocytes contains the third fibronectin type 3 (FNIII) repeat but lacks the mucin-like domain which supports the view that neurofascin isoforms are differentially expressed in the nervous system. Among the genes that are up-regulated during the terminal differentiation of the oligodendrocyte, neurofascin is unique in displaying a transient pattern of expression at the early stages of myelination. We propose that this CAM not only has a role in mediating axon recognition but also signals axonal contact through its links with the actin cytoskeleton.
Collinson
J M
JM
Department of Preclinical Veterinary Sciences, University of Edinburgh, Scotland.
Marshall
D
D
Gillespie
C S
CS
Brophy
P J
PJ
D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000502:physiology*; D001921:Brain / Q000166:cytology / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002450:Cell Communication / Q000502:physiology; D002478:Cells, Cultured; D015723:Gene Library; D017404:In Situ Hybridization, Fluorescence; D007365:Intercellular Junctions / Q000502:physiology; D009186:Myelin Sheath / Q000502:physiology*; D009414:Nerve Growth Factors / Q000096:biosynthesis*; D009457:Neuroglia / Q000166:cytology / Q000502:physiology*; D009836:Oligodendroglia / Q000166:cytology / Q000502:physiology*; D015347:RNA Probes; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000166:cytology / Q000502:physiology
D015815:Cell Adhesion Molecules; D009414:Nerve Growth Factors; C504594:Nfasc protein, rat; D015347:RNA Probes