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© The Rockefeller University Press, 0021-9525/1997//1123 $5.00
The Journal of Cell Biology, Volume 136, Number 5, , 1997 1123-1136

Article

Establishment of the Dorso-ventral Axis in Xenopus Embryos Is Presaged by Early Asymmetries in β-Catenin That Are Modulated by the Wnt Signaling Pathway



Carolyn A. Larabell§, Monica Torres*, Brian A. Rowning*,§,||, Cynthia Yost{ddagger}, Jeffrey R. Miller*, Mike Wu||, David Kimelman{ddagger}, and Randall T. Moon*

* Howard Hughes Medical Institute and Department of Pharmacology, {ddagger} Department of Biochemistry, University of Washington School of Medicine, Seattle, Washington 98195; and § Lawrence Berkeley National Laboratory, || Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California 94720

Eggs of Xenopus laevis undergo a postfertilization cortical rotation that specifies the position of the dorso-ventral axis and activates a transplantable dorsal-determining activity in dorsal blastomeres by the 32-cell stage. There have heretofore been no reported dorso-ventral asymmetries in endogenous signaling proteins that may be involved in this dorsal-determining activity during early cleavage stages. We focused on β-catenin as a candidate for an asymmetrically localized dorsal-determining factor since it is both necessary and sufficient for dorsal axis formation. We report that β-catenin displays greater cytoplasmic accumulation on the future dorsal side of the Xenopus embryo by the two-cell stage. This asymmetry persists and increases through early cleavage stages, with β-catenin accumulating in dorsal but not ventral nuclei by the 16- to 32cell stages. We then investigated which potential signaling factors and pathways are capable of modulating the steady-state levels of endogenous β-catenin. Steadystate levels and nuclear accumulation of β-catenin increased in response to ectopic Xenopus Wnt-8 (Xwnt-8) and to the inhibition of glycogen synthase kinase-3, whereas neither Xwnt-5A, BVg1, nor noggin increased β-catenin levels before the mid-blastula stage. As greater levels and nuclear accumulation of β-catenin on the future dorsal side of the embryo correlate with the induction of specific dorsal genes, our data suggest that early asymmetries in β-catenin presage and may specify dorso-ventral differences in gene expression and cell fate. Our data further support the hypothesis that these dorso-ventral differences in β-catenin arise in response to the postfertilization activation of a signaling pathway that involves Xenopus glycogen synthase kinase-3.

Abbreviations used in this paper: DAM, dorsal animal marginal; dnXgsk-3, dominant negative (kinase-dead) Xenopus glycogen synthase kinase-3; DVM, dorsal vegetal marginal; MBT, mid-blastula transition; MeOH, methanol; ptβ-catenin-myc, point mutant in β-catenin-myc; VAM, ventral animal marginal; VVM, ventral vegetal marginal; Xgsk-3, Xenopus glycogen synthase kinase-3; Xwnt, Xenopus Wnt.

M. Torres, J. Miller, and R. Moon were supported by the Howard Hughes Medical Institute, and B. Rowning (HD27525 and HD 29360 to R.T. Moon), C. Yost (GM 07270), and D. Kimelman (HD27262) were supported by Public Health Service Awards from the National Institutes of Health. C. Larabell was supported by the Office of Health and Environmental Research, U.S. Department of Energy.

Note Added in Proof. β-Catenin was translated in vitro and labeled with [35S]methionine (as in Yost et al., 1996), then comparable amounts were injected into either dorsal or ventral blastomeres of four-cell embryos. Monitoring the injected β-catenin by SDS-PAGE and autoradiography demonstrates that it is more stable on the dorsal side of the embryo, as predicted by our experiments presented here and in Yost et al. (1996).

Address all correspondence to Randall T. Moon, Howard Hughes Medical Institute, Campus Box 357370, Room K536C Health Sciences Building, University of Washington School of Medicine, Seattle, WA 98195. Tel.: (206) 543-1722. Fax: (206) 543-0858.rtmoon{at}u.washington.edu


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