title: Timing of endogenous activin-like signals and regional specification of the Xenopus embryo.
abstract: Signaling by activin-like ligands is important for induction and patterning of mesoderm and endoderm. We have used an antibody that specifically recognizes the phosphorylated and activated form of Smad2, an intracellular transducer of activin-like ligands, to examine how this signaling pathway patterns the early mesendoderm. In contrast to the simple expectation that activin-like signaling should be highest on the dorsal side of the gastrula stage embryo, we have found that while Smad2 phosphorylation is highest dorsally before gastrulation, signaling is attenuated dorsally and is highest on the ventral side by mid-gastrulation. Early dorsal initiation of Smad2 phosphorylation results from cooperation between the vegetally localized maternal transcription factor VegT and dorsally localized beta-catenin. The subsequent ventral appearance of Smad2 phosphorylation is dependent on VegT, but not on signaling from the dorsal side. Dorsal attenuation of Smad2 phosphorylation during gastrulation is mediated by early dorsal expression of feedback inhibitors of activin-like signals. In addition to regulation of Smad2 phosphorylation by the expression of activin-like ligands and their antagonists, the responsiveness of embryonic cells to activin-like ligands is also temporally regulated. Ectopic Vg1, Xnr1 and derrière all fail to activate Smad2 phosphorylation until after the midblastula transition, and the onset of responsiveness to these ligands is independent of transcription. Furthermore, the timing of cellular responsiveness differs for Xnr1 and derrière, and these distinct temporal patterns of responsiveness can be correlated with their distinctive phenotypic effects. These observations suggest that the timing of endogenous activin-like signaling is a determinant of patterning in the early Xenopus embryo.
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Lee
authors.forename: J
authors.initials: J
authors.lastname: Heasman
authors.forename: M
authors.initials: M
authors.lastname: Whitman
mesh_terms: D028341:Activins; D000818:Animals; D000906:Antibodies / Q000276:immunology; D019521:Body Patterning / Q000502:physiology; D002454:Cell Differentiation; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D004707:Endoderm / Q000378:metabolism; D007265:Inhibins / Q000378:metabolism*; D008024:Ligands; D008648:Mesoderm / Q000378:metabolism; D008954:Models, Biological; D010766:Phosphorylation; D015398:Signal Transduction; D051899:Smad2 Protein; D020825:T-Box Domain Proteins / Q000378:metabolism; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014981:Xenopus; D029867:Xenopus Proteins; D051176:beta Catenin
chemical_list: D000906:Antibodies; C495266:CTNNB1 protein, Xenopus; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D008024:Ligands; D051899:Smad2 Protein; C497785:Smad2 protein, Xenopus; D020825:T-Box Domain Proteins; D015534:Trans-Activators; C103966:VegT protein, Xenopus; D029867:Xenopus Proteins; D051176:beta Catenin; D028341:Activins; D007265:Inhibins