| First Author | Hu QD | Year | 2003 |
| Journal | Cell | Volume | 115 |
| Issue | 2 | Pages | 163-75 |
| PubMed ID | 14567914 | Mgi Jnum | J:86140 |
| Mgi Id | MGI:2678866 | Doi | 10.1016/s0092-8674(03)00810-9 |
| Citation | Hu QD, et al. (2003) F3/contactin acts as a functional ligand for Notch during oligodendrocyte maturation. Cell 115(2):163-75 |
| abstractText | 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 gamma-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. |
