@article{0d3796cd641944a88114b7344e4367d8,
title = "F3/contactin acts as a functional ligand for notch during oligodendrocyte maturation",
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.",
author = "Hu, {Qi Dong} and Ang, {Beng Ti} and Meliha Karsak and Hu, {Wei Ping} and Cui, {Xiao Ying} and Tanya Duka and Yasuo Takeda and Wendy Chia and Natesan Sankar and Ng, {Yee Kong} and Ling, {Eng Ang} and Thomas Maciag and Deena Small and Radianna Trifonova and Raphael Kopan and Hideyuki Okano and Masato Nakafuku and Shigeru Chiba and Hisamaru Hirai and Aster, {Jon C.} and Melitta Schachner and Pallen, {Catherine J.} and Kazutada Watanabe and Xiao, {Zhi Cheng}",
note = "Funding Information: We particularly thank Dr. Jeffrey Nye for providing mouse Notch1 cDNA, and Dr. Genevieve Rougon for the F3-transfected CHO cell line and F3 antibody, and for extensive discussion on the project and critical review of the manuscript. We also thank Dr. Domna Karagogeos for providing TAG-1- and TAX-transfected CHO cell lines, Dr. Melanie Richter for CHL1-Fc, Dr. Urban Lendahl for Notch1, and Notch3 antibodies, Dr. Tetsuo Sudo (Toray, Japan) for Hes1 polyclonal antibody, Dr. Ryoichiro Kageyama for pGVB/Hes1 luciferase reporter construct, and Dr. Craig Heilman for wild-type RBP-J construct. We are particularly indebted to Alain Israel for long-term support and critique on our work and providing murine Notch1-transfected HeLa cells and NICD antibody. We sincerely thank Dr. Malcolm Paterson for insightful comments and revision of the manuscript. We are grateful to Dr. Yun-Jin Jiang for his valuable suggestion. This work was supported by grants from: (1) the National Medical Research Council of Singapore, Singapore Health Services Pte Ltd., and Department of Clinical Research, Singapore General Hospital to Z.C. Xiao; (2) Canadian Institutes of Health Research to C.J. Pallen; (3) the Hertie Foundation and the European Community to M. Schachner; and (4) NIH grants HL 35627, HL 32348, and RR 15555 to T. Maciag.",
year = "2003",
month = oct,
day = "17",
doi = "10.1016/S0092-8674(03)00810-9",
language = "English",
volume = "115",
pages = "163--175",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "2",
}