title: Temporal mapping of the differentiation pathway of the murine erythroleukemia cell.
abstract: These studies are concerned with "mapping" the temporal order of the precommitment events in the differentiation pathway of the Friend erythroleukemia cell. We have used a single-block procedure in which a differentiation-specific inhibitor of a temperature-sensitive (ts) differentiation-defective mutation was used to block the differentiation program. Later, the block was removed, differentiation was allowed to proceed, and the time required to reach a reference marker was monitored. These studies have indicated that the mutations tsC2GP1 and tsB5A, the poly(ADP-ribose) polymerase inhibitor 3-aminobenzamide, and the glucocorticoid hormone dexamethasone blocked functions which are required just prior to commitment. We have also used a double-block procedure involving two consecutive restrictive conditions, which suggests that the 3-aminobenzamide- and tsC2GP1-blocked functions constitute a part of a sequentially ordered pathway leading to terminal differentiation. The convergence of the 3-aminobenzamide, dexamethasone, and ts mutational blocks just prior to commitment suggests that the blocked functions may be part of a major control mechanism for commitment. In these studies, we have introduced a cytochalasin B-based assay to monitor commitment. The use of cytochalasin B permits a direct assay for commitment and obviates the need for colony-forming assays using semisolid medium, which have inherent problems such as efficiency of plating.
authors.affiliation: Department of Microbiology and Immunology, University of Western Ontario, London, Canada.
authors.forename: K
authors.initials: K
authors.lastname: Ebisuzaki
authors.forename: W L
authors.initials: WL
authors.lastname: Casley
authors.forename: A
authors.initials: A
authors.lastname: Griffiths
authors.forename: L
authors.initials: L
authors.lastname: Wheaton
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D003571:Cytochalasin B / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005622:Friend murine leukemia virus; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology*; D051379:Mice; D009154:Mutation; D014407:Tumor Cells, Cultured
chemical_list: D003571:Cytochalasin B; D003907:Dexamethasone; D004121:Dimethyl Sulfoxide