ACTIVIN HAS DIRECT LONG-RANGE SIGNALING ACTIVITY AND CAN FORM A CONCENTRATION GRADIENT BY DIFFUSION

Background: Activin has strong mesoderm-inducing properties in the ear ly Xenopus embryo, and has a long-range signalling activity that activ ates genes in cells distant from a source in a concentration-dependent way. It has not yet been established what mechanism of signal transmi ssion accounts for this and other examples of long-range signalling in vertebrates. Nor is it known whether activin itself acts on distant c ells or whether other kinds of molecules are used for long-range signa lling, Here we have used a well characterised model system, involving animal caps of Xenopus blastulae treated with activin or transforming growth factor beta, to analyze some fundamental properties of long-ran ge signalling and of the formation of a morphogen gradient. Results: W e find that cells distant from the source of activin require functiona l activin receptors to activate Xbrachyury, a result suggesting that a ctivin itself acts directly on distant cells and that other secondary signalling molecules are not required. We also find that the signals c an be transmitted across a tissue that cannot respond to it; this argu es against a relay process. We provide direct evidence that labelled a ctivin forms a concentration gradient emanating from its source and ex tending to the distant cells that express Xbrachyury, Lastly, we show that there is no inherent polarity in the responding tissue that influ ences either the direction or rate of signalling, Conclusions: The lon g-range signalling mechanism by which activin initiates the transcript ion of genes in a concentration-dependent manner depends on a process of rapid diffusion and the establishment of an activin gradient across the tissue. It cannot be explained by a relay or wave propagation mec hanism. Activin itself is the signalling molecule to which distant cel ls respond.