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Title: F3/contactin acts as a functional ligand for notch during oligodendrocyte maturation
Authors: Hu, Q.-D.
Ang, B.-T. 
Cui, X.-Y.
Duka, T.
Chia, W.
Xiao, Z.-C. 
Ng, Y.-K. 
Ling, E.-A. 
Karsak, M.
Schachner, M.
Hu, W.-P.
Takeda, Y.
Watanabe, K.
Sankar, N.
Maciag, T.
Small, D.
Trifonova, R.
Kopan, R.
Okano, H.
Nakafuku, M.
Chiba, S.
Hirai, H.
Aster, J.C.
Pallen, C.J.
Issue Date: 2003
Citation: Hu, Q.-D., Ang, B.-T., Cui, X.-Y., Duka, T., Chia, W., Xiao, Z.-C., Ng, Y.-K., Ling, E.-A., Karsak, M., Schachner, M., Hu, W.-P., Takeda, Y., Watanabe, K., Sankar, N., Maciag, T., Small, D., Trifonova, R., Kopan, R., Okano, H., Nakafuku, M., Chiba, S., Hirai, H., Aster, J.C., Pallen, C.J. (2003). F3/contactin acts as a functional ligand for notch during oligodendrocyte maturation. Cell 115 (2) : 163-175. ScholarBank@NUS Repository.
Abstract: Axon-derived molecules are temporally and spatially required as positive or negative signals to coordinate oligodendrocyte differentiation. Increasing evidence suggests that, in addition to the inhibitory Jagged1/Notch1 signaling cascade, other pathways act via Notch to mediate oligodendrocyte differentiation. The GPI-linked neural cell recognition molecule F3/contactin is clustered during development at the paranodal region, a vital site for axoglial interaction. Here, we show that F3/contactin acts as a functional ligand of Notch. This trans-extracellular interaction triggers γ-secretase-dependent nuclear translocation of the Notch intracellular domain. F3/Notch signaling promotes oligodendrocyte precursor cell differentiation and upregulates the myelin-related protein MAG in OLN-93 cells. This can be blocked by dominant negative Notch1, Notch2, and two Deltex1 mutants lacking the RING-H2 finger motif, but not by dominant-negative RBP-J or Hes1 antisense oligonucleotides. Expression of constitutively active Notch1 or Notch2 does not upregulate MAG. Thus, F3/contactin specifically initiates a Notch/Deltex1 signaling pathway that promotes oligodendrocyte maturation and myelination.
Source Title: Cell
ISSN: 00928674
DOI: 10.1016/S0092-8674(03)00810-9
Appears in Collections:Staff Publications

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