Housekeeping by chemokine scavenging.

restoring fucosylation. In the absence of fucose, the FX / mice display a profound neutrophilia. Part of this neutrophilia can be explained by loss of selectin ligands (Sialyl Lewis x contains fucose), but proliferation of myeloid progenitor cells suggests that myelopoiesis is being stimulated. Zhou and coworkers have now examined the proliferation of myeloid lineages in FX / mice and attributed it to loss of fucose-dependent Notch activation in myeloid progenitors. The authors present compelling data that suggests a role for Notch activation in suppression of myeloid differentiation, a somewhat controversial area. Another recent publication highlighted the importance of O-fucose at a specific site on Notch1 in T-cell development.4 Ge and Stanley generated a mouse in which endogenous Notch1 was replaced with a mutant lacking the O-fucosylation site in the ligand-binding domain (within EGF repeat 12). Homozygotes developed fairly normally but had a reduced number of T cells, suggesting that Ofucosylation of Notch1 at EGF repeat 12 is important for T-cell development. These results raise a number of interesting questions. All 4 receptors should be unfucosylated in FX / mice, but it is not known which Notch receptor is responsible for suppression of myeloproliferation. As mentioned, modification of O-fucose by Fringe modulates Notch activity. In the absence of Fringe, Ofucose remains a monosaccharide, but in the presence of Fringe it is elongated to a tetrasaccharide. The relevant structures of the Ofucose glycans that are lost in FX / mice are unknown. Because O-fucosylation of EGF repeat 12 in Notch1 plays such an important role in T-cell development, it would be interesting to know if loss of this specific fucose also suppresses myelogenesis. The future of Notch and hematopoiesis certainly looks sweet. Conflict-of-interest disclosure: The author declares no competing financial interests. ■