title: Sirenomelia in Bmp7 and Tsg compound mutant mice: requirement for Bmp signaling in the development of ventral posterior mesoderm.
abstract: Sirenomelia or mermaid-like phenotype is one of the principal human congenital malformations that can be traced back to the stage of gastrulation. Sirenomelia is characterized by the fusion of the two hindlimbs into a single one. In the mouse, sirens have been observed in crosses between specific strains and as the consequence of mutations that increase retinoic acid levels. We report that the loss of bone morphogenetic protein 7 (Bmp7) in combination with a half dose or complete loss of twisted gastrulation (Tsg) causes sirenomelia in the mouse. Tsg is a Bmp- and chordin-binding protein that has multiple effects on Bmp metabolism in the extracellular space; Bmp7 is one of many Bmps and is shown here to bind to Tsg. In Xenopus, co-injection of Tsg and Bmp7 morpholino oligonucleotides (MO) has a synergistic effect, greatly inhibiting formation of ventral mesoderm and ventral fin tissue. In the mouse, molecular marker studies indicate that the sirenomelia phenotype is associated with a defect in the formation of ventroposterior mesoderm. These experiments demonstrate that dorsoventral patterning of the mouse posterior mesoderm is regulated by Bmp signaling, as is the case in other vertebrates. Sirens result from a fusion of the hindlimb buds caused by a defect in the formation of ventral mesoderm.
authors.affiliation: Howard Hughes Medical Institute, and Department of Biological Chemistry, University of California, Los Angeles, CA 90095-1662, USA.
authors.forename: Lise
authors.initials: L
authors.lastname: Zakin
authors.forename: Bruno
authors.initials: B
authors.lastname: Reversade
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kuroda
authors.forename: Karen M
authors.initials: KM
authors.lastname: Lyons
authors.forename: Eddy M
authors.initials: EM
authors.lastname: De Robertis
mesh_terms: D000818:Animals; D015153:Blotting, Western / Q000662:veterinary; D019521:Body Patterning / Q000502:physiology; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000235:genetics* / Q000378:metabolism; D004480:Ectromelia / Q000196:embryology / Q000235:genetics / Q000662:veterinary*; D018507:Gene Expression Regulation, Developmental; D006614:Hindlimb / Q000473:pathology; D006652:Histological Techniques / Q000662:veterinary; D017403:In Situ Hybridization / Q000662:veterinary; D008648:Mesoderm / Q000502:physiology*; D051379:Mice; D009154:Mutation / Q000235:genetics; D016376:Oligonucleotides, Antisense; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary; D012376:Rodent Diseases / Q000196:embryology* / Q000235:genetics; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism; D014981:Xenopus; D029867:Xenopus Proteins
chemical_list: C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D016376:Oligonucleotides, Antisense; D011506:Proteins; D016212:Transforming Growth Factor beta; D029867:Xenopus Proteins; C525822:bmp7.1 protein, Xenopus; C473561:twisted gastrulation protein, mouse