title: Effects of heterodimerization and proteolytic processing on Derrière and Nodal activity: implications for mesoderm induction in Xenopus.
abstract: Derrière is a recently discovered member of the TGFbeta superfamily that can induce mesoderm in explant assays and is expressed at the right time and location to mediate mesoderm induction in response to VegT during Xenopus embryogenesis. We show that the ability of Derrière to induce dorsal or ventral mesoderm depends strictly on the location of expression and that a dominant-negative Derrière cleavage mutant completely blocks all mesoderm formation when ectopically expressed. This differs from the activity of similar Xnr2 cleavage mutant constructs, which are secreted and retain signaling activity. Additional analysis of mesoderm induction by Derrière and members of the Nodal family indicates that these molecules are involved in a mutual positive-feedback loop and antagonism of either one of the signals can reduce the other. Interaction between Derrière and members of the Nodal family is also shown to occur through the formation of heterodimeric ligands. Using an oocyte expression system we show direct interaction between the mature Derrière ligand and members of both the Nodal and BMP families. Taken together, these findings indicate that Derrière and Nodal proteins probably work cooperatively to induce mesoderm throughout the marginal zone during early Xenopus development.
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3202, USA.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Eimon
authors.forename: Richard M
authors.initials: RM
authors.lastname: Harland
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019281:Dimerization; D004625:Embryo, Nonmammalian; D004627:Embryonic Induction; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005799:Genes, Dominant; D006133:Growth Substances / Q000235:genetics / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins; D008648:Mesoderm; D008969:Molecular Sequence Data; D055457:Nodal Protein; D055456:Nodal Signaling Ligands; D011506:Proteins; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D014981:Xenopus / Q000196:embryology* / Q000235:genetics; D029867:Xenopus Proteins
chemical_list: C118849:GDF3 protein, Xenopus; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; C113775:Ndr2 protein, vertebrate; D055457:Nodal Protein; D055456:Nodal Signaling Ligands; D011506:Proteins; C485173:STK38L protein, Xenopus; D016212:Transforming Growth Factor beta; D029867:Xenopus Proteins