Sirenomelia in Bmp7 and Tsg compound mutant mice

Requirement for Bmp signaling in the development of ventral posterior mesoderm

Lise Zakin, Bruno Reversade, Hiroki Kuroda, Karen M. Lyons, Eddy M. De Robertis

Research output: Contribution to journalArticle

58 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2489-2499
Number of pages11
JournalDevelopment
Volume132
Issue number10
DOIs
Publication statusPublished - 2005 May
Externally publishedYes

Fingerprint

Ectromelia
Bone Morphogenetic Protein 7
Gastrulation
Mesoderm
Hindlimb
Phenotype
Morpholinos
Extracellular Space
Xenopus
Tretinoin
Vertebrates
Carrier Proteins
Mutation
Injections

Keywords

  • Bmp
  • Bmp4
  • Chordin
  • Dorsoventral patterning
  • Limb bud
  • Morpholino
  • Mouse
  • Sirenomelia
  • TGFβ
  • Twisted gastrulation (Twsg1)
  • Xenopus

ASJC Scopus subject areas

  • Anatomy
  • Cell Biology

Cite this

Sirenomelia in Bmp7 and Tsg compound mutant mice : Requirement for Bmp signaling in the development of ventral posterior mesoderm. / Zakin, Lise; Reversade, Bruno; Kuroda, Hiroki; Lyons, Karen M.; De Robertis, Eddy M.

In: Development, Vol. 132, No. 10, 05.2005, p. 2489-2499.

Research output: Contribution to journalArticle

Zakin, Lise ; Reversade, Bruno ; Kuroda, Hiroki ; Lyons, Karen M. ; De Robertis, Eddy M. / Sirenomelia in Bmp7 and Tsg compound mutant mice : Requirement for Bmp signaling in the development of ventral posterior mesoderm. In: Development. 2005 ; Vol. 132, No. 10. pp. 2489-2499.
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