Cnidarians and the evolution of bilaterality

The sea anemone Nematostella vectensis is a very interesting species. Its life cycle consists
of female adults that spawn egg packages of several hundred eggs into the water, which are
then fertilized by the sperm given into the water by male animals. The eggs develop into
cysts which can last quite a long time. When the cyst develops, for example when a scientist
forces it to, a gastrula forms after 24 hours. After three days, a planual larvae has developed,
which again quickly develops into a primary polyp. This is finished after 7 days.
It only takes a few months for the animal to become sexually mature.
What is even more interesting, though, is the fact that these animals show a bilateral axis
already while in the planula larvae stadium!
This is quite unusual. Normally, the key bilaterian traits are the bilaterality (naturally), a
mesoderm, and a central nervous system. Up until now, the cnidaria, as diploblasts, were
not counted among the bilaterians.

Now, how does the oral-aboral axis of the cnidarians relate to the anterior-posterior and the
dorsal-ventral axis of bilateria?
In 1939, Sven Hörstadius published an experiment he did with the embryos of sea urchins.
He cut the embryos in the 8-cell-stadium in half - some along the animal-vegetal axis and
some perpendicular to it. The embryos which had two animal cells and two vegetal cells
each developed normally, albeit half as big as usual. The ones that has no vegetal cells left,
just the four animal cells, did not develop properly. The ones with only vegetal cells
developed normally.
He concluded that only the vegetal half of the embryo has the capabilities to form a whole
organism.
When Prof. Technau and his group did this experiment with Nematosella embryos, they
found that the exact opposite was true. Only the animal half of the embryo had the
capabilities to form a whole polyp.
So, while in amphibians, transplantation of the dorsal vegetal cells (Nieuwkoop center) or of
the Spemann organizer cells induces the formation of twin body axes, meaning that localised
determinants determine the lateral axis, in Nematostella, only the blastopore lip can induce
the ectopic axes.
Even more exactly, a specific part at the bend of the blastopore lip has axis-inducing
capacity. The highest activity of the determinants is in the second "slice", where the lip is
thickest.
What are the molecular workings behind this?
In frogs, injecting Wnt enzymes had same effect as the transplantation. APC -/- mosaic
CRISPR mutants show various degrees of ectopic head formation. APC stops the Wnt-Chain.
Therefore, Wnt/beta-catenin signaling appears to be the best candidate for the role of the
regulator of the oral identity along the O-A-axis.
This Oral-aboral axis patterning by Wnt signaling may relate to posterior-anterior axis
patterning of Bilateria. There seems to be a conserved role for beta catenin in establishing
primary body axis and gastrulation site; this occurs even in sponges.
The blastopore organizer likely evolved in the eumetazoan ancestor, rather than in the
deuterostomia.
But what about the dorsal/ventral axis?
The dorso-ventral expression patterns of Sog/Chordin and Dpp/BMP4 are conserved
between Drosophila and vertebrates. There is always more Sog/Chordin in the area where
the central nervous system lies (dorsal for vertebrates, ventral for Drosophila).
And there is an evidence for second body axis in Nematostella: A symmetry break of chordin
and dpp during the blastopore stadium. This symmetry break in the expression of BMP
signaling is BMP dependent. Two opposing signaling centers with BMPs and BMP antagonists
pattern the directive axis. The resulting pSMAD1/5 gradient has its maximum opposite to
DPP.
Also, there is a bilaterality in sea anemones: The position of the retractor muscles is
asymmetric.
A knockdown of BMP or antagonists drastically affects pSMAD1/5 gradient and the
formation of the eight mesenteries.
In summary, there are conserved factors in the formation of the body axes, but they act in
different positions in Nematosella and in vertebrates like frogs.
Mathematical models recapitulated the experimental data to see how strongly each
parameter can change before the system collapses. The result is that some parameters are
highly constrained, others not so much. BAMBI, Gdf5, Grm are more free to evolve than the
others, and weakly constrained modulators are more replacable, resulting in different forms.
Nematostella Hox genes are also expressed in staggered domains along the directive axis
and dependent on BMP signaling. These staggered Hox genes downstream of BMP signaling
gradient mark boundaries of mesenteries along the directive axis. The direction of the BMP
signaling gradient is defined by expression of chordin, not by expression of bmp4.
Also, there is no phylogenetic information in the expression localisation: they are diffusive
molecules, what matters is the localisation of the signaling.