title: Linear signaling in the Toll-Dorsal pathway of Drosophila: activated Pelle kinase specifies all threshold outputs of gene expression while the bHLH protein Twist specifies a subset.
abstract: Differential activation of the Toll receptor leads to the formation of a broad Dorsal nuclear gradient that specifies at least three patterning thresholds of gene activity along the dorsoventral axis of precellular embryos. We investigate the activities of the Pelle kinase and Twist basic helix-loop-helix (bHLH) transcription factor in transducing Toll signaling. Pelle functions downstream of Toll to release Dorsal from the Cactus inhibitor. Twist is an immediate-early gene that is activated upon entry of Dorsal into nuclei. Transgenes misexpressing Pelle and Twist were introduced into different mutant backgrounds and the patterning activities were visualized using various target genes that respond to different thresholds of Toll-Dorsal signaling. These studies suggest that an anteroposterior gradient of Pelle kinase activity is sufficient to generate all known Toll-Dorsal patterning thresholds and that Twist can function as a gradient morphogen to establish at least two distinct dorsoventral patterning thresholds. We discuss how the Dorsal gradient system can be modified during metazoan evolution and conclude that Dorsal-Twist interactions are distinct from the interplay between Bicoid and Hunchback, which pattern the anteroposterior axis.
authors.affiliation: Department of Molecular and Cell Biology, Division of Genetics and Development, 401 Barker Hall, University of California, Berkeley, CA 94720, USA.
authors.forename: Angelike
authors.initials: A
authors.lastname: Stathopoulos
authors.forename: Michael
authors.initials: M
authors.lastname: Levine
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D019521:Body Patterning / Q000235:genetics; D004330:Drosophila / Q000196:embryology* / Q000235:genetics* / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D004789:Enzyme Activation; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D018257:Helix-Loop-Helix Motifs; D017403:In Situ Hybridization; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction; D051193:Toll-Like Receptors; D014157:Transcription Factors; D051879:Twist-Related Protein 1
chemical_list: D029721:Drosophila Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011956:Receptors, Cell Surface; C068721:Tl protein, Drosophila; D051193:Toll-Like Receptors; D014157:Transcription Factors; C497753:Twi protein, Drosophila; D051879:Twist-Related Protein 1; C062236:dl protein, Drosophila; C079896:pll protein, Drosophila; D017346:Protein Serine-Threonine Kinases