Review
The canonical Wnt pathway in embryonic axis polarity

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Abstract

The canonical Wnt pathway plays crucial roles in multiple developmental processes, including in axis specification. Throughout the animal kingdom, this pathway has been reported to drive patterning of axes as different as the animal–vegetal axis in echinoderms to the dorsal–ventral axis in vertebrates. Intriguingly enough, this pathway appears structurally and functionally well conserved during evolution. However, differences between these phyla are observed that explain how a same pathway can mediate establishment of two such apparently distinct axes. This review compares the axis specification processes used in two evolutionarily distant embryos, the sea urchin and Xenopus.

Introduction

One of the earliest and most important steps occurring during development of all organisms is the establishment of the embryonic axes. In few species, including Drosophila, body axes specification takes place before fertilization [1], while in others, such as the nematode Caenorhabditis elegans, these axes are set up only after fertilization [2]. However, in most organisms, including echinoderms and vertebrates, the first embryonic axis, the animal–vegetal axis, is determined during oogenesis while the dorso–ventral axis is established after fertilization. Many experiments have clearly demonstrated that specification along the embryonic axes is always dictated by polarities established before and/or after fertilization by a combination of localized maternal determinants and cellular interactions. One pathway that has been strongly implicated in axis formation in all phyla is the canonical Wnt pathway. From the diploblast Hydra to the vertebrates, this pathway is among the most evolutionarily well conserved [3], [4]. It is required in a wide variety of cell interactions that play fundamental roles in multiple processes including cell-fate specification, determination of cell polarity and cell migration, and tumorogenesis [5].

In the past decade, the role of the canonical Wnt pathway in axis specification has been best characterized in sea urchin and Xenopus [6], [7]. In each organism, components of the pathway are synthesized during oogenesis, then required shortly after fertilization to specify a critical embryonic axis. In sea urchin the canonical Wnt pathway mediates the specification of the animal–vegetal (AV) axis; whereas, in Xenopus, it is necessary for the establishment of the dorsal–ventral (DV) axis, a completely different axis that is perpendicular to the initial AV polarity. Nevertheless, the mechanisms used by the canonical pathway in both sea urchin and frog to create these axes, respectively, appears to be structurally and functionally well conserved; cytoplasmic and nuclear molecules involved are identical as are their interactions. However, small but nevertheless important differences occur external to or within the pathway that explain why these two distinct axes are formed. After a brief description of the general mechanism of the canonical Wnt signaling, this review will discuss how this pathway is used by two evolutionarily distant organisms, the sea urchin and Xenopus, to specify their embryonic axes.

Section snippets

An overview of the canonical Wnt pathway

Wnt signaling can activate three distinct downstream pathways, the canonical β-catenin-dependent pathway, and two non-canonical pathways. This review however will focus only on the canonical pathway. In general, secreted Wnt ligands act on neighbouring cells, rather than diffusing broadly [8], [9], [10]. The Wnt genes glycoproteins are characterized by special features such as an invariant pattern of 23 highly conserved cysteines residues, twelve of which lie in the last 70 C-terminal

Wnt signaling and the animal–vegetal axis in sea urchin

In sea urchins, the maternally derived canonical Wnt pathway is required to pattern the animal–vegetal (AV) axis. Prior to fertilization, sea urchin oocytes possess a primordial AV polarity that was demonstrated in the past by several embryological experiments [40], [41], [42]. Those experiments further indicated that after fertilization cytoplasmic rearrangements are minimal in sea urchin eggs causing this AV polarity to remain as the first embryonic AV axis (Fig. 2). In addition, in the

Wnt signaling and the dorso–ventral axis in Xenopus

In Xenopus, as in most deuterostomes embryos, the canonical Wnt pathway is required to specify the dorso–ventral (DV) axis, which is established perpendicularly to the primordial AV axis. Experiments performed with various key components of the pathway have demonstrated that, in this organism as in sea urchin, the same cytoplasmic and nuclear molecules, including Dsh, Gsk3β, β-catenin and TCF/LEF, are involved and that they interact and regulate each other in the same way [53], [54].

Conclusion and prospects

The general picture emerging from the above findings is that despite important evolutionary differences, i.e. the dorsal relocalization of Dsh and Wnt11 proteins in response to cortical rotation in Xenopus, many similarities exist between the establishment of the AV axis in echinoderms and the DV axis in vertebrates. In both phyla, specification of these axes is controlled shortly after fertilization by the canonical Wnt pathway which appears structurally and functionally well conserved.

Acknowledgments

The authors acknowledge Athula Wikramanayake, Christian Gache and Thierry Lepage for discussing data ahead of publication. We also thank Drs. Cynthia Bradham and Christine Byrum for critical evaluation of the manuscript. The authors are supported by grants NIH 61464 and HD 14483.

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