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.

FCC may predict the steepness of individual motor gains. Future training could therefore focus on directly inducing these beneficial increases in FC. Evaluation of the treatment groups suggests that MI is a potential facilitator of such neuroplasticity.

Cancer has long been viewed as a heterogeneous population of cells. While the great majority of cells that make up tumors are destined to differentiate, albeit aberrantly, and eventually stop dividing, only a minority population of cells, termed cancer stem cells, possess extensive self-renewal capability and can recapitulate tumor pathophysiology in an immune-compromised animal model. Tumor-initiating cells have been identified and isolated in a variety of cancers of the blood, breast, central nervous system, pancreas, skin, head and neck, colon, and prostate. In this review we present scientific evidence supporting the cancer stem cell model of tumor progression, and discuss the experimental and therapeutic implications. The concept of cancer stem cells may have profound implications for our understanding of tumor biology and for the design of novel treatments targeted toward these cells. Current therapeutic strategies include targeting the cancer stem cell as well as its microenvironmental niche. We present an interesting, novel strategy that takes into account the reactive oxygen species status in cancer stem cells and how it might serve as a method for eradicating these cells in tumor growth.