title: The evolutionarily conserved BMP-binding protein Twisted gastrulation promotes BMP signalling.
abstract: Dorsal-ventral patterning in vertebrate and Drosophila embryos requires a conserved system of extracellular proteins to generate a positional information gradient. The components involved include bone morphogenetic proteins (BMP/Dpp), a BMP antagonist (Chordin/Short gastrulation; Chd/Sog) and a secreted metalloproteinase (Xolloid/Tolloid) that cleaves Chd/Sog. Here we describe Xenopus Twisted gastrulation (xTsg), another member of this signalling pathway. xTsg is expressed ventrally as part of the BMP-4 synexpression group and encodes a secreted BMP-binding protein that is a BMP signalling agonist. The data suggest a molecular mechanism by which xTsg dislodges latent BMPs bound to Chordin BMP-binding fragments generated by Xolloid cleavage, providing a permissive signal that allows high BMP signalling in the embryo. Drosophila Tsg also binds BMPs and is expressed dorsally, supporting the proposal that the dorsal-ventral axis was inverted in the course of animal evolution.
authors.affiliation: Howard Hughes Medical Institute and Department of Biological Chemistry, University of California, Los Angeles 90095-1662, USA.
authors.forename: M
authors.initials: M
authors.lastname: Oelgeschläger
authors.forename: J
authors.initials: J
authors.lastname: Larraín
authors.forename: D
authors.initials: D
authors.lastname: Geissert
authors.forename: E M
authors.initials: EM
authors.lastname: De Robertis
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D005075:Biological Evolution; D019521:Body Patterning / Q000502:physiology; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002460:Cell Line; D017124:Conserved Sequence; D029721:Drosophila Proteins; D006023:Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D011485:Protein Binding; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014981:Xenopus; D029867:Xenopus Proteins
chemical_list: C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D029721:Drosophila Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; C090223:TSG protein, Drosophila; D029867:Xenopus Proteins; C525812:bmp4 protein, Xenopus; C054234:chordin