What the papers say
Hox genes in a pentameral animal
Ellen Popodi* and Rudolf A. Raff
Summary
There is renewed interest in how the different body plans
of extant phyla are related. This question has traditionally
been addressed by comparisons between vertebrates
and Drosophila. Fortunately, there is now increasing
emphasis on animals representing other phyla. Pentamerally symmetric echinoderms are a bilaterian metazoan
phylum whose members exhibit secondarily derived
radial symmetry. Precisely how their radially symmetric
body plan originated from a bilaterally symmetric ancestor is unkown, however, two recent papers address
this subject. Peterson et al.(1) propose a hypothesis on
evolution of the anteroposterior axis in echinoderms,
and Arenas-Mena et al.(2) examine expression of five posterior Hox genes during development of the adult sea
urchin. BioEssays 23:211±214, 2001. ß 2001 John Wiley
& Sons, Inc.
Animal body plans
Although there are over three million living animal species,
there are only 35 major body plans (phyla). These body plans
had arisen by about 540 million years ago, marking the
Cambrian radiation, in which animal body plans appear in
profusion in the fossil record. Although they are profoundly
different from each other, all animal groups descend from a
single common ancestor and, hence, are all branches of a
single metazoan phylogenetic tree. The vast majority of these
phyla are bilaterally symmetrical (bilaterians), with three major
body axes: anteroposterior (AP), dorsoventral (DV) and left±
right (LR). Bilaterians are divided into two major superphyla,
the deuterostomes (chordates, echinoderms and hemichordates) and the protostomes (arthropods, mollusks, annelids
and several other phyla). The nature of the common deuterostome±protostome ancestor, and how body plan transformations took place pose major questions.
Recent revisions to the phylogenetic tree based on molecular analyses and re-evaluation of morphology, have provided a framework for new views on the relationships of these
body plans.(3,4) The renewed support for a close relationship
between the echinoderms and the bilaterally symmetric hemichordates is important to this particular story. (5±8)
All metazoans share a common set of regulatory genes,
and aspects of the expression of these genes appear to have
been conserved over hundreds of millions of years of animal
Department of Biology, Indiana University, Bloomington, IN 47405.
*Correspondence to: Ellen Popodi, Department of Biology, Indiana
University, Bloomington, IN 47405.
BioEssays 23:211±214, ß 2001 John Wiley & Sons, Inc.
evolution. This information has resulted in revision and revitalization of old hypotheses linking the body plans of the
protostomes and deuterostomes. The expression of patterning molecules important in DV patterning supports the idea of
that DV inversion occurred in embryogenesis in the ancestor of
one of these two clades (for a discussion of this point, see
Ref. 9). There are a number of genes that pattern along the AP
axis, which is easily recognized in most bilaterian phyla. Adult
echinoderms, however, showing pentameral symmetry, appear to lack this axis.
Hox genes and body axes
Hox genes are ubiquitous among animal phyla, and are widely
and centrally involved in spatial regulation along the AP axis in
animal development.(10) The regulation of major spatial patterning decisions by Hox genes have been studied most extensively in insects and mammals,(11,12) and show three highly
conserved features. (1) Hox genes are organized into clusters
that are conserved in their general gene composition (nine
basic Hox genes or paralog groups) and order.(13± 16) (2) Hox
genes are expressed colinearily, in the same order along the
body axis as their order in the cluster. Thus, in order of anteriorto-posterior expression domains there are anterior, middle,
and posterior group genes. (3) A large portion of the AP body
axis of bilaterians is patterned by Hox genes.(10,17)
The pentameral and apparently headless Echinodermata
have diverged radically from the basic bilaterian body plan,
making it difficult to recognize the ancestral axes. Over the
decades there have been several scenarios put forward for the
evolution of this body plan.(1,18± 23) It is hoped that the retention
of some of the ancestral gene expression patterns important in
patterning the body during development might help elucidate
the relationship of the echinoderm body plan to that of other
bilaterian phyla. Recent reports(1,2) indicate that Hox gene
patterns might reveal AP axial components in echinoderm
development.
Sea urchins have been used extensively as model organisms for the study of fertilization and early embryonic development. A large number of genes have been cloned and there is
an effort underway to sequence the genome of one species,
Strongylocentrotus purpuratus.(24) The life cycle of sea urchins
(and most other echinoderms) includes a larval stage that is
usually planktonic and planktotrophic. Adult structures form in
a rudiment on the left side of the otherwise bilaterally symmetric larva. A vast amount of molecular information has been
amassed on the early embryonic development of the sea
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What the papers say
urchin larva. Recently more attention has been turned toward
the development of adult structures and the developmental
processes involved in making the pentameral adult.
The genomes of sea urchins (and other echinoderms)
contain many of the same regulatory genes that play major
developmental roles in chordates. The functions and expression patterns during development of the adult body of several
of these have been investigated (otx, engrailed,(25) Brachyury,
Not,(26) Wnt genes,(27) distalless, Ref. 28).
Sea urchins have a single Hox cluster(29) containing paralogs of almost all of the vertebrate Hox genes. So far ten Hox
genes have been identified(30) representing genes belonging
to anterior (paralog groups 1, 2, 3); medial (paralog groups 4,
5, 6, 7, 8) and posterior (paralog groups 9, 10, 11, 12, 13, 14)
groups. Six of these Hox genes are clear representatives of
paralog groups 1, 2, 3, 6, 7, 8. Four genes that most resemble
combinations of adjacent paralog groups (based on sequence
and position in the cluster) are designated Hox4/5, Hox9/10,
Hox11/13a and Hox11/13b. Recent PCR analyses in other
echinoderms suggest that there may be additional echinoderm
Hox genes.(31,32) Whether sea urchins have representatives
of these additional Hox genes will become clear as the sea
urchin genome sequencing project is completed.(24) All ten of
the known sea urchin Hox genes are transcribed during formation of the pentameral adult whereas only two are transcribed during development of the bilaterial pluteus larva.(33)
Hypothesizing the location of the AP axis
in echinoderms
The hypothesis of Peterson et al.(1) on the relationship of
the echinoderm body plan to other bilaterian body plans is
diagrammed in Fig. 1. The authors ``propose a new interpretation of axial homologies in echinoderms employing three lines
of evidence.'' The criteria considered are the expression
patterns of two Hox genes in coeloms, SpHox11/13b(1) and
SpHox3,(33) the anatomy of certain fossil echinoderms, and
the relation between endoskeletal plate morphology and the
associated coelomic tissues. The hypothesis suggests that
the adult mouth is anterior and that AP axis runs from the
mouth through the adult coelomic compartments. In the larva,
coeloms are bilaterally oriented on either side of the gut.
Metamorphosis to the adult form involves torsion such that
these coeloms become stacked right on top of left. The
hypothesis of coelomic stacking posits that the originally
paired and AP-oriented coeloms of the ancestral deuterostome have become torted and stacked during the evolution
of the adult echinoderm body plan.(1)
Tracing Hox gene expression patterns
in sea urchins
Arenas-Mena et al.(2) report the expression pattern of five
consecutive Hox genes from the 5 0 (posterior) end of the Hox
cluster (Hox7 to Hox11/13b) during the period of rudiment
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formation in sea urchins. This paper adds to an earlier report
describing the timing of expression of these genes and the
pattern of expression of a Hox3 homologue.(33) Their expression patterns are striking and fit with their model discussed
above.
Remarkably, spatial co-linearity was observed. A spatially
sequential pattern of expression of the five ``posterior'' Hox
genes examined was observed in the bilaterally arranged,
mesodermally derived somatocoels. The expression patterns
overlapped and followed a vector that traced the curvature of
the digestive tract. If, as the authors point out, the digestive
tract were straightened out, the pattern would be very similar to
AP patterns in the neurectoderm and mesoderm of chordates.
Based on a model presented by Peterson et al.(1) the pattern in
sea urchin predicts that the Hox genes will be sequentially
expressed in the coeloms of the hemichordates.
As adult development proceeds the rudiment enlarges, the
somatocoels lose their bilaterally symmetric character and the
pattern of Hox expression becomes increasingly asymmetric
with more expression in left-side structures. This also fits with
the hypothesis of coelomic stacking.
What is unexpected about the observed sequential pattern
is that it is found in the mesodermal somatocoels only. In the
other bilaterians examined, the Hox genes exhibit sequential
expression in both the mesoderm and the ectoderm or neurectoderm. This raises intriguing possibilities. Did echinoderms lose or reduce ectodermal or neurectodermal structures
that ancestrally expressed the Hox genes? Did the ancestral
bilaterian exhibit co-linear expression of Hox genes in mesodermal structures only, with co-linear ectodermal expression
acquired independently in the two major clades? Analysis of
the expression patterns of the remaining Hox genes and of
other patterning genes may provide insights into these question, and contribute to a theory for the evolution of the echinoderm body plan that accounts for the morphological and
gene expression transformations that have taken place.
Arenas-Mena et al.(2) also discovered numerous examples
of apparent co-options to non-axial patterns of expression
unique to echinoderms, such as spines and test plates. These
involved only a subset of the Hox genes examined, not the
entire cluster, and did not show the temporal and spatial colinearity that is a hallmark of the AP pattern of Hox expression
in other phyla. This is consistent with a number of other gene
co-option events identified in echinoderms.(25,34)
What about the pentameral parts?
The axial patterns of expression of the posterior group Hox
genes reported by Arenas-Mena et al.(2) are confined to the
somatocoel mesoderm. Three important questions remain
before we can unravel the history of the echinoderm body plan.
First, most of the adult echinoderm body is pentameral.
We have little idea of how pentamery is generated in development. The only evidence thus far of Hox gene involvement in
What the papers say
Figure 1. Larval structure, coelomic stacking and posterior Hox gene expression. A: Diagrams of ventral and left views of a
generalized echinoderm larva showing the position of the gut, coeloms and rudiment. For clarity, the coeloms were omitted in the leftside view. B: Block diagrams indicating the relationship of the coeloms to the gut in a generalized echinoderm larva and an echinoid (sea
urchin) adult. Drawings are based on Figures 2 and 3 of Peterson et al.(1) C: Generalized diagram of the order of posterior Hox gene
expression in the left somatocoel. The expression patterns of these genes broadly overlap, this is not shown. The white arrow indicates
development of pentameral structures is that Hox3 is
expressed in the dental sacs that give rise to the adult mouth
parts.(32) No functional role is known. Second, in most animals
examined, the central nervous system (CNS) also expresses
an AP Hox expression pattern, and this expression represents
a major feature of bilaterian axial patterning. The centralized
part of the echinoderm nervous system consists of a
circumoral (or circumanal in the case of crinoids) ring
connecting five radial nerve trunks that run out along each
arm of the animal. There is little evidence for Hox gene
expression in sea urchin CNS at this point. We have almost no
data, however, on the patterns of expression and inferred roles
for the anterior genes of the Hox cluster in echinoderms. The
posterior group genes are expressed in non-pentameral
coelomic mesoderm. The expression pattern of Hox3 suggests that anterior Hox genes may be involved in pentamerally
symmetric structures.
The possible lack of Hox gene expression in the adult CNS
is suggestive. If the echinoderm CNS is derived from part or all
of the ancestral CNS, there are several possibilities. The
circumoral and radial CNS of echinoids may represent a small
portion of the ancestral bilaterian CNS derived from a region
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What the papers say
anterior to much or all of the Hox patterning domain. In such a
case, we would expect to find genes characteristic of the most
anterior domain of the AP axis, such as otx and forkhead. A
corollary to this hypothesis would be that the circumanal and
radial nervous system of crinoids derived from a posterior
portion of the ancestral bilaterian CNS and, therefore, would
be expected to express a different set of patterning genes. It is
also possible that the echinoderm CNS is a novel structure not
directly derived from the ancestral bilaterian CNS. These
possibilities show how little we still know, and just how strange
the bilaterian-to-echinoderm transition may have been.
We look forward to additional gene patterns, particularly the
anterior Hox genes and other regulatory genes that have
conserved roles in anterior structures in other phyla. Expression patterns in several classes of echinoderms will be needed. Such information will provide further tests of the currently
proposed models and may enable speculation on what, if any,
echinoderm structures may have derived from ancestral
anterior regions. We also need to see patterns in the sister
bilaterian taxon of echinoderms, the hemichordates. The
fledgling work describing expression patterns in this
group(35,36) will provide necessary outgroup information.
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