Signalling by TGF-beta family members: short-range effects of Xnr-2 and BMP-4 contrast with the long-range effects of activin

Curr Biol. 1996 Nov 1;6(11):1468-75. doi: 10.1016/s0960-9822(96)00751-8.


Background: One way of establishing a morphogen gradient in a developing embryo involves the localized synthesis of an inducing molecule followed by its diffusion into surrounding tissues. The morphogen-like effects of the mesoderm-inducing factor activin provide support for this idea in amphibian development. The questions remain, however, of how activin exerts its long-range effects, and whether long-range signalling is a property of all transforming growth factor beta (TGF-beta) family members.

Results: We compare the signalling ranges of activin and two other TGF-beta family members, Xnr-2 and BMP-4. Unlike activin, Xnr-2 and BMP-4 act over short distances. Furthermore, the effects of constitutively active activin receptors are strictly cell-autonomous. These observations suggest that the long-range effects of activin occur through protein diffusion and that "relay' mechanisms are not initiated by any of these TGF-beta family members. Mechanisms limiting the signalling range of Xnr-2 were addressed by studying Xnr-2 processing and secretion. An activin-Xnr-2 fusion protein signals over many cell diameters, suggesting that regulated processing or secretion is one limiting factor. Disaggregation and reaggregation of Xnr-2-producing tissues also extends the range of Xnr-2, suggesting that components of intact tissue restrict spread of the protein.

Conclusions: The long-range effects of activin are likely to occur through the diffusion of activin protein. The short-range effects of Xnr-2 and BMP-4 emphasize that long-range diffusion is not a general property of TGF-beta-related molecules. Finally, signalling ranges may be regulated by constraints on processing or secretion and by interactions with extracellular components of embryonic tissues.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activin Receptors, Type I
  • Activins
  • Animals
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Proteins / genetics
  • Bone Morphogenetic Proteins / metabolism*
  • DNA-Binding Proteins / metabolism
  • Fetal Proteins / metabolism
  • Goosecoid Protein
  • Homeodomain Proteins*
  • Inhibins / genetics
  • Inhibins / metabolism*
  • Mice
  • Nodal Signaling Ligands
  • Proteins / genetics
  • Proteins / metabolism*
  • Receptors, Growth Factor / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Repressor Proteins*
  • Signal Transduction / physiology*
  • T-Box Domain Proteins*
  • Transcription Factors*
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism*
  • Xenopus
  • Xenopus Proteins*


  • Bmp4 protein, mouse
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Proteins
  • DNA-Binding Proteins
  • Fetal Proteins
  • Goosecoid Protein
  • Gsc protein, mouse
  • Homeodomain Proteins
  • Ndr2 protein, vertebrate
  • Nodal Signaling Ligands
  • Proteins
  • Receptors, Growth Factor
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • STK38L protein, Xenopus
  • T-Box Domain Proteins
  • Transcription Factors
  • Transforming Growth Factor beta
  • Xenopus Proteins
  • bmp4 protein, Xenopus
  • Activins
  • Inhibins
  • Activin Receptors, Type I
  • Brachyury protein