Molecular investigations of the origin of the dorso-ventral axis in an obscure marine invertebrate illuminate one of the longest-running debates in evolutionary biology — that over the origin of vertebrates.
Vertebrates are so different from other creatures that discovering their origins within the animal kingdom has always been problematic. But molecular, developmental and genomic work on the sometimes obscure invertebrate relatives of vertebrates is prompting a re-evaluation of this vexed topic.
As they recount in PLoS Biology, Lowe et al.1 have been looking at the expression of genes associated with the specification of the dorso-ventral body axis — which surface becomes the upper (back) body surface and which the lower (belly) — in Saccoglossus kowalevskii, a worm-like member of the hemichordates. This is a group that is distantly related to the chordates, the larger group to which vertebrates themselves belong (Fig. 1). The authors find that the dorso-ventral axis in hemichordates is specified in a similar way to that in other animals. But this axis is decoupled from the development of the central nervous system — a later, chordate elaboration not found in hemichordates. This implies that the rules governing dorso-ventral axis formation are ancient and probably evolved with the first bilaterally symmetrical (bilaterian) multicellular animals.
The quest to understand the deployment of the dorso-ventral axis has been one of the most enduring themes in the study of vertebrate origins. It stems from the time of the wayward nineteenth-century savant Etienne Geoffroy Saint-Hilaire, who proposed that insects have the same basic body plan as vertebrates, only turned upside-down2. This notion joined a list of seemingly eccentric theories about vertebrate origins that has been lengthening ever since3. Another is the idea that vertebrates have independently invented a new kind of mouth on the opposite body surface to that in other animals. A third is that chordates and hemichordates evolved directly from ancestors akin to extinct, asymmetrical echinoderms (the group that includes modern sea-urchins and starfishes), some of which seem to have sported the characteristic gill slits seen today in chordates and, as it happens, hemichordates.
Molecular work has disposed of most of these ideas — but not without highlighting valuable grains of truth in each of them. For example, construction of molecular evolutionary trees4 revitalized an old idea5 that echinoderms and hemichordates are sister taxa, in which case some primitive echinoderms really did have gill slits, no longer apparent in modern forms. Likewise, the discovery6 that insects have a genetic system of dorso-ventral specification similar to that of vertebrates — only inverted — gave Geoffroy Saint-Hilaire a new celebrity. Lowe et al.1 build on this idea by showing that hemichordates exploit this same system in their development based on an axial polarity between two types of patterning molecule — BMP (bone morphogenetic protein) at one pole, and Chordin and its affiliates at the other. Baldly put, the dorso-ventral axis in all complex animals is determined largely by the antagonistic relationship of these two groups of agent.
In insects such as Drosophila, BMP is associated with what is conventionally regarded as the dorsal surface in the adult animal. In chordates, by contrast, BMP is a ventralizing agent. The inversion, however, is more apparent than real, having been determined after the fact by using the central nervous system — conventionally dorsal in chordates but ventral in insects — as a primary reference for telling which way is up.
Lowe and colleagues' work1 on hemichordates adds welcome perspective. Because hemichordates have a diffuse nerve net rather than a central nervous system, this reference point disappears. Instead, we see that chordates differ from all other animals — hemichordates as well as insects — in the position of the mouth, which is relocated to the Chordin side of the animal, rather than the BMP side. In this way, some of the old ideas, in which vertebrates were defined by the presence of a new mouth, had a basis in fact, however coincidentally. More seriously, this new perspective will prompt a reappraisal of the many peculiarities of the development of the mouth that are seen in lampreys (primitive, jawless vertebrates) and amphioxus (a primitive, non-vertebrate chordate). However, the central nervous systems of insects and chordates — and indeed those of all animals that have them — represent a range of solutions in which the location is governed by the BMP–Chordin axis, if not directly specified by them.
Lowe et al.1 also show that in hemichordates, as in insects, dorso-ventral patterning is independent of the patterning of the anterior–posterior axis. That this is not true in chordates highlights another special feature of the latter group, perhaps associated with the development of a distinct embryonic 'organizer'. This feature has very deep roots in chordates, and is now being investigated in amphioxus7.
The status of amphioxus itself has likewise been a matter of debate. A chordate that is conventionally regarded as the closest invertebrate relative of vertebrates, it seems8 that it may be the most primitive known extant chordate, and thus key to our understanding of chordate innovations, including the organizer. Such a status has brought this shy creature back into a limelight it has not enjoyed since the 1930s. The amphioxus genome is not far off completion, and when it arrives it will be in select company: the genome of another primitive chordate — the tunicate Ciona intestinalis — has been described9, and that of a sea-urchin, Strongylocentrotus purpuratus, an echinoderm long used in developmental studies, has just been announced10.
Of course, sequencing a genome is not the same as understanding the evolution of morphological novelties. But we have come a long way since 1909, when the Linnean Society of London convened a symposium on vertebrate origins to celebrate the golden jubilee of the publication of Darwin's Origin of Species, and at which one participant ruefully remarked11: “When we return home and our friends gleefully enquire, 'What then has been decided as to the Origin of Vertebrates?', so far we seem to have no reply ready, except that the disputants agreed on one single point, namely that their opponents were all in the wrong.”
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Henry Gee is a Senior Editor of Nature.
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Theory in Biosciences (2011)