GRADED AMOUNTS OF XENOPUS DISHEVELLED SPECIFY DISCRETE ANTEROPOSTERIOR CELL FATES IN PROSPECTIVE ECTODERM

Signals emitted from the prospective dorsal marginal zone (the organiz er) are thought to specify neuroectodermal cell fates along the antero posterior (AP) axis, but the mechanisms underlying this signaling even t remain to be elucidated. To assess the effect of Xenopus Dishevelled (Xdsh), a proposed component of the Wnt, Notch and Frizzled signal tr ansduction pathways, on AP axis determination, it was supplied in vary ing doses to presumptive ectodermal cells. Two-fold increments in leve ls of microinjected Xdsh mRNA revealed a gradual shift in cell fates a long the AP axis. Lower doses of Xdsh mRNA activated anterior neuroect odermal markers, XAG1 and Xotx2, whereas the higher doses induced more posterior neural tissue markers such as En2, Krox20 and HoxB9. At the highest dose of Xdsh mRNA, explants contained maximal amount of HoxB9 transcripts and developed notochord and somites. When compared with X dsh, Xwnt8 mRNA also activated anterior neuroectodermal markers, but f ailed to elicit mesoderm formation. Analysis of explants overexpressin g Xdsh at the gastrula stage revealed activation of several organizer- specific genes which have been implicated in determination of neural t issue (Xotx2, noggin, chordin and follistatin). Whereas Goosecoid, Xli m1 and Xwnt8 were not induced in these explants, another early margina l zone marker, Xbra, was activated at the highest level of Xdsh mRNA. These observations suggest that the effects of Xdsh on AP axis specifi cation may be mediated by combinatorial action of several early patter ning genes. Increasing levels of Xdsh mRNA activate posterior markers, whereas increasing amounts of the organizer stimulate the extent of a nterior development (Stewart, R.M. and Gerhart, J.C. (1990) Developmen t 109, 363-372). These findings argue against induction of the entire organizer by Xdsh in ectodermal cells and implicate signal transductio n pathways involving Xdsh in AP axis determination. Thus, different le vels of a single molecule, Xdsh, can specify distinct cell states alon g the AP axis. (C) 1997 Elsevier Science Ireland Ltd.