title: GSK3 is a multifunctional regulator of Dictyostelium development.
abstract: Glycogen synthase kinase 3 (GSK3) is a central regulator of metazoan development and the Dictyostelium GSK3 homologue, GskA, also controls cellular differentiation. The originally derived gskA-null mutant exhibits a severe pattern formation defect. It forms very large numbers of pre-basal disc cells at the expense of the prespore population. This defect arises early during multicellular development, making it impossible to examine later functions of GskA. We report the analysis of a gskA-null mutant, generated in a different parental strain, that proceeds through development to form mature fruiting bodies. In this strain, Ax2/gskA-, early development is accelerated and slug migration greatly curtailed. In a monolayer assay of stalk cell formation, the Ax2/gskA- strain is hypersensitive to the stalk cell-inducing action of DIF-1 but largely refractory to the repressive effect exerted by extracellular cAMP. During normal development, apically situated prestalk cells express the ecmB gene just as they commit themselves to stalk cell differentiation. In the Ax2/gskA- mutant, ecmB is expressed throughout the prestalk region of the slug, suggesting that GskA forms part of the repressive signalling pathway that prevents premature commitment to stalk cell differentiation. GskA may also play an inductive developmental role, because microarray analysis identifies a large gene family, the 2C family, that require gskA for optimal expression. These observations show that GskA functions throughout Dictyostelium development, to regulate several key aspects of cellular patterning.
authors.affiliation: School of Life Sciences, Wellcome Trust Biocentre, University of Dundee, Dundee DD1 5EH, UK.
authors.forename: Christina
authors.initials: C
authors.lastname: Schilde
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Araki
authors.forename: Hazel
authors.initials: H
authors.lastname: Williams
authors.forename: Adrian
authors.initials: A
authors.lastname: Harwood
authors.forename: Jeffrey G
authors.initials: JG
authors.lastname: Williams
mesh_terms: D000362:Agar; D000595:Amino Acid Sequence; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects; D002999:Clone Cells / Q000502:physiology; D000242:Cyclic AMP / Q000494:pharmacology; D004023:Dictyostelium / Q000166:cytology / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development*; D016326:Extracellular Matrix Proteins / Q000235:genetics; D017353:Gene Deletion; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D050791:STAT Transcription Factors; D016415:Sequence Alignment; D015398:Signal Transduction; D033761:Spores, Protozoan / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016326:Extracellular Matrix Proteins; D015800:Protozoan Proteins; D050791:STAT Transcription Factors; C426583:STATa protein, Dictyostelium; D014157:Transcription Factors; C069214:ecmB protein, Dictyostelium; D000362:Agar; D000242:Cyclic AMP; D038362:Glycogen Synthase Kinase 3