title: Tsukushi functions as an organizer inducer by inhibition of BMP activity in cooperation with chordin.
abstract: During chick gastrulation, inhibition of BMP signaling is required for primitive streak formation and induction of Hensen's node. We have identified a unique secreted protein, Tsukushi (TSK), which belongs to the Small Leucine-Rich Proteoglycan (SLRP) family and is expressed in the primitive streak and Hensen's node. Grafts of cells expressing TSK in combination with the middle primitive streak induce an ectopic Hensen's node, while electroporation of TSK siRNA inhibits induction of the node. In Xenopus embryos, TSK can block BMP function and induce a secondary dorsal axis, while it can dorsalize ventral mesoderm and induce neural tissue in embryonic explants. Biochemical analysis shows that TSK binds directly to both BMP and chordin and forms a ternary complex with them. These observations indicate that TSK is an essential dorsalizing factor involved in the induction of Hensen's node.
authors.affiliation: Department of Developmental Neurobiology Graduate School of Medical Sciences.|PRESTO, JST 4-1-8 Honcho Kawaguchi Saitama 332-0012 Japan.
authors.forename: Kunimasa
authors.initials: K
authors.lastname: Ohta
authors.affiliation: Department of Anatomy University of Cambridge Downing Street Cambridge CB2 3DY United Kingdom.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lupo
authors.affiliation: Department of Developmental Neurobiology Graduate School of Medical Sciences.|21 Century COE Kumamoto University Kumamoto 860-8556 Japan.
authors.forename: Sei
authors.initials: S
authors.lastname: Kuriyama
authors.affiliation: Department of Anatomy University of Cambridge Downing Street Cambridge CB2 3DY United Kingdom.
authors.forename: Roger
authors.initials: R
authors.lastname: Keynes
authors.affiliation: Department of Anatomy University of Cambridge Downing Street Cambridge CB2 3DY United Kingdom.
authors.forename: Christine E
authors.initials: CE
authors.lastname: Holt
authors.affiliation: Department of Anatomy University of Cambridge Downing Street Cambridge CB2 3DY United Kingdom.
authors.forename: William A
authors.initials: WA
authors.lastname: Harris
authors.affiliation: Department of Developmental Neurobiology Graduate School of Medical Sciences.|21 Century COE Kumamoto University Kumamoto 860-8556 Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Department of Oncology The Hutchison/MRC Research Centre University of Cambridge Hills Road Cambridge CB2 2XZ United Kingdom.
authors.forename: Shin-Ichi
authors.initials: SI
authors.lastname: Ohnuma
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002642:Chick Embryo; D003001:Cloning, Molecular; D005775:Gastrula / Q000166:cytology; D018507:Gene Expression Regulation, Developmental; D015723:Gene Library; D006023:Glycoproteins / Q000378:metabolism*; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D007908:Lens, Crystalline / Q000196:embryology; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D011485:Protein Binding; D011509:Proteoglycans / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014981:Xenopus; D029867:Xenopus Proteins
chemical_list: D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D011509:Proteoglycans; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D029867:Xenopus Proteins; C525812:bmp4 protein, Xenopus; C054234:chordin