Members of the Wnt and TGF-beta superfamilies regulate both cell fate and proliferation during development and tissue maintenance. In the early amphibian embryo, the Wnt and TGF-beta superfamily signalling cascades are required for the establishment of a dorsal signalling centre, Spemann's organizer. Intracellular proteins of both pathways, upon activation, translocate to the nucleus to participate in transcription. Here we show that beta-catenin and Lef1/Tcf, which are downstream components of the Wnt signalling cascade, form a complex with Smad4, an essential mediator of signals initiated by members of the TGF-beta growth factor superfamily. In Xenopus, this interaction directly and synergistically affects expression of the twin (Xtwn) gene during formation of the organizer. This is, to our knowledge, the first demonstration of a physical interaction between TGF-beta and Wnt signalling components in vivo.

The multicatalytic proteinase complex is a multi-subunit, high molecular weight proteinase present in the nucleus and cytoplasm of eukaryotic cells. This catalytic complex is involved in diverse cellular functions as part of the ubiquitin proteolysis system, including non-lysosomal proteolysis, antigen presentation, cell cycle progression, and cell proliferation, and in the programmed death of intersegmental muscles after adult eclosion in the tobacco hornworm moth, Manduca sexta. We have investigated the distribution of the multicatalytic proteinase complex in the central nervous system of this moth. At all stages of post-embryonic development, most cell types exhibited consistent, low levels of cytoplasmic and nuclear immunoreactivity for the multicatalytic proteinase complex. High levels of cell-specific accumulation of the complex were, however, demonstrated in abdominal neurosecretory cells and in imaginal cells in the larval brain, the larval segmental ganglia, and the developing wing discs. Imaginal cells exhibited intense immunoreactivity for the multicatalytic proteinase complex only until the onset of terminal differentiation. Intersegmental muscles undergoing programmed cell death exhibited intense cytoplasmic immunoreactivity for the multicatalytic proteinase, while persisting flight muscles and dying neurons were characterized by basal levels of staining. These staining patterns suggest that the multicatalytic proteinase of Manduca sexta serves multiple functions and is associated with the period of developmental arrest displayed by imaginal cells prior to metamorphosis.