Distinct requirements for extra-embryonic and embryonic bone morphogenetic protein 4 in the formation of the node and primitive streak and coordination of left-right asymmetry in the mouse

Development. 2002 Oct;129(20):4685-96.

Abstract

In the mouse and chick embryo, the node plays a central role in generating left-right (LR) positional information. Using several different strategies, we provide evidence in the mouse that bone morphogenetic protein 4 (Bmp4) is required independently in two different sites for node morphogenesis and for LR patterning. Bmp4 expression in the trophoblast-derived extra-embryonic ectoderm is essential for the normal formation of the node and primitive streak. However, tetraploid chimera analysis demonstrates that Bmp4 made in epiblast-derived tissues is required for robust LR patterning, even when normal node morphology is restored. In the absence of embryonic Bmp4, the expression of left-side determinants such as Nodal and Lefty2 is absent in the left lateral plate mesoderm (LPM). Noggin-mediated inhibition of Bmp activity in cultured wild-type embryos results in suppression of Nodal expression in the LPM. Thus, unlike previous models proposed in the chick embryo in which Bmp4 suppresses left-sided gene expression, our results suggest that Bmp acts as a positive facilitator of the left-sided molecular cascade and is required for Nodal induction and maintenance in the left LPM.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Body Patterning / genetics*
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Proteins / genetics
  • Bone Morphogenetic Proteins / metabolism*
  • Ectoderm / metabolism
  • Fibroblast Growth Factor 8
  • Fibroblast Growth Factors / genetics
  • Fibroblast Growth Factors / metabolism
  • Gene Expression Regulation, Developmental
  • Head / embryology
  • Heart / embryology
  • Intercellular Signaling Peptides and Proteins
  • Left-Right Determination Factors
  • Mesoderm / metabolism
  • Mice
  • Mice, Mutant Strains
  • Mutation
  • Nodal Protein
  • Proteins / genetics
  • Proteins / metabolism
  • Signal Transduction
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism

Substances

  • Bmp4 protein, mouse
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Proteins
  • Dte protein, mouse
  • Fgf8 protein, mouse
  • Intercellular Signaling Peptides and Proteins
  • Left-Right Determination Factors
  • Nodal Protein
  • Nodal protein, mouse
  • Proteins
  • Transforming Growth Factor beta
  • fibroblast growth factor 14
  • Fibroblast Growth Factor 8
  • Fibroblast Growth Factors