Xenopus Embryo: β‐catenin and Dorsal–Ventral Axis Formation

Abstract

During embryonic development of the amphibian, Xenopus laevis, the dorsal side of the embryo forms approximately opposite the sperm entry point, and the anterior and posterior axes are linked to this through the process of gastrulation. The mechanisms responsible for specification of the dorsal axis include a post‐fertilization cortical rotation that promotes a dorsal accumulation of β‐catenin, and the activation of a cascade of regulatory genes by the complexes of β‐catenin and HMG box transcription factors that start the process of gastrulation.

Keywords: Xenopus; embryo; gene expression; axis; β‐catenin

Figure 1.

Overview of how fertilization leads to establishment of the dorsal axis in Xenopus embryos. (a) In the unfertilized egg there is no dorsal–ventral polarity, (b) Fertilization anywhere within the animal (upper) hemisphere stimulates a rotation of approximately 30° of the cortex relative to the cytoplasm. This is dependent upon microtubule tracks in the vegetal pole. Vesicles, likely with associated Dsh and GBP, move from the vegetal pole 60–90° to the future dorsal side, opposite the sperm entry point, (c) GSK‐3 activity is suppressed on the dorsal side. While it is unknown whether the regulation of GSK‐3 activity upon fertilization involves any Wnt and Fz signalling from the membrane, it is thought to be dependent upon the dorsal accumulation of Dsh and GBP, (d) β‐catenin is synthesized throughout the egg, but is degraded on the ventral side in response to phosphorylation of β‐catenin by CK1 and GSK‐3, which targets it to ubiquitination and degradation by the proteosome, (e) Since β‐catenin is more stable on the prospective dorsal side of the embryo, it accumulates in the cytoplasm, (f) As β‐catenin accumulates, it enters nuclei, where it forms complexes with the HMG box transcription factor Tcf, (g) Complexes of β‐catenin and Tcf bind to the promoter of the homeobox gene siamois, directly inducing its expression on the dorsal side, leading to induction of additional genes required to form the Spemann organizer. (Circles denote cells expressing siamosis.)

Figure 2.

Wnt/β‐catenin signalling pathway in vertebrates. In the absence of Wnt signals (left), newly synthesized β‐catenin either binds to cadherins at the plasma membrane, or is phosphorylated by CK1 then GSK‐3, probably in a degradation complex containing Axin and APC, leading to its being ubiquitinated and degraded by the proteosome. In the presence of Wnt signals, the Wnt receptor Fz and LRP‐5/6 co‐receptor signalling leads to activation of Dishevelled (Dsh), which then acts at least in part via GBP to suppress the activity of GSK‐3. With GSK‐3 suppressed, β‐catenin accumulates, enters nuclei and forms complexes with Tcf and LEF family members (X) which then regulate gene expression (arrows in nucleus denotes gene activation). α, α‐catenin; β, β‐catenin; P, phosphate. (Adapted with permission from Miller and Moon ; more complete model at http://www.stanford.edu/%7Ernusse/wntwindow.html. Copyright © 1996 Cold Spring Harbor Laboratory Press.)

Figure 3.

Dorsal accumulation of β‐catenin in Xenopus embryos. Confocal microscopic image of β‐catenin in a four‐cell Xenopus embryo. β‐catenin (orange) accumulates in the cytoplasm on the prospective dorsal side of the embryo (right) opposite the sperm entry point (left). Green is autofluorescence of yolk. (Reproduced from Larabell et al.. Copyright, The Rockerfeller University Press.)

close

References

Brannon M, Gomperts M, Sumoy L, Moon RT and Kimelman D (1997) A β‐catenin/Xtcf‐3 complex binds to the siamoispromoter to regulate dorsal axis specification in Xenopus. Genes and Development 11: 2359–2370.

Cadigan KM and Nusse R (1997) Wnt signaling: a common theme in animal development. Genes and Development 11: 3286–3305.

Gerhart JC, Danilchik M, Doniach T, et al. (1989) Cortical rotation of the Xenopusegg: consequences for the anteroposterior pattern of embryonic dorsal development. Development 107(Suppl.): 37–51.

Harland R and Gerhart J (1997) Formation and function of Spemann's organizer. Annual Review of Cell and Developmental Biology 13: 611–667.

Heasman J (1997) Patterning the Xenopusblastula. Development 12: 2155–2164.

Heasman J, Crawford A and Goldstone K (1994) Overexpression of cadherins and underexpression of β‐catenin inhibit dorsal mesoderm induction in early Xenopus embryos. Cell 79: 791–803.

Kessler DS and Melton DA (1995) Induction of dorsal mesoderm by soluble, mature Vg1 protein. Development 12: 2155–2164.

Larabell CA, Torres M, Rowning BA, et al. (1997) Establishment of the dorso‐ventral axis in Xenopus embryos is presaged by early asymmetries in β ‐catenin which are modulated by Wnt signalling. Journal of Cell Biology 136: 1123–1136.

Lemaire P, Garrett N and Gurdon JB (1995) Expression cloning of siamois, a Xenopus homeobox gene expressed in dorsal‐vegetal cells of blastulae and able to induce a complete secondary axis. Cell 81: 85–94.

Miller JR and Moon RT (1996) Signal transduction through β‐catenin and specification of cell fate during embryogenesis. Genes and Development 10: 2527–2539.

Miller JR, Rowning BA, Larabell CA, et al. (1999) Establishment of the dorsal–ventral axis in Xenopus embryos coincides with the dorsal enrichment of Dishevelled that is dependent on cortical rotation. Journal of Cell Biology 146: 427–437.

Molenaar M, van de Wetering M and Oosterwegel M (1996) Xtcf‐3 transcription factor mediates β‐catenin induced axis formation in Xenopus embryos. Cell 86: 391–399.

Moon RT and Kimelman D (1998) From cortical rotation to organizer gene expression: toward a molecular explanation of axis specification in Xenopus. BioEssays 20: 536–545.

Morin PJ, Sparks AB and Korinek V (1997) Activation of β‐catenin‐Tcf signaling in colon cancer by mutations in β‐catenin or APC. Science 275: 1787–1790.

Rubinfeld B, Robbins P, El‐Gamil M, et al. (1997) Stabilization of β‐catenin by genetic defects in melanoma cell lines. Science 275: 1790–1794.

Watabe T, Kim S, Candia A, et al. (1995) Molecular mechanisms of Spemann's organizer formation: conserved growth factor synergy between Xenopus and mouse. Genes and Development 9: 3038–3050.

Weaver C and Kimelman D (2004) Move it or lose it: axis specification in Xenopus Development. 131: 3491–3499.

Yost C, Torres M, Miller JR, et al. (1996) The axis‐inducing activity, stability, and subcellular distribution of β‐catenin is regulated in Xenopus embryos by glycogen synthase kinase 3. Genes and Development 10: 1443–1454.

Further Reading

Cadigan KM and Nusse R (1997) Wnt signaling: a common theme in animal development. Genes and Development 11: 3286–3305.

Heasman J (1997) Patterning the Xenopusblastula. Development 12: 2155–2164.

Moon RT and Kimelman D (1998) From cortical rotation to organizer gene expression: toward a molecular explanation of axis specification in Xenopus. BioEssays 20: 536–545.

Weaver C, Farr GH, Pan W, et al. (2003) GBP binds kinesin light chain and translocates during cortical rotation in Xenopus eggs. Development 130: 5425–5436.

Wnt homepage http://www.stanford.edu/%7Ernusse/wntwindow.html

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Moon, Randall T(Sep 2005) Xenopus Embryo: β‐catenin and Dorsal–Ventral Axis Formation. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0004185]