Adult polyp of the sea anemone Nematostella vectensis.
Grigory Genikhovich
Bodybuilding in Ancient Times: How the Sea Anemone Got Its Back
Childish creationist claims of a young Earth, the spontaneous magical generation of all living organisms without ancestry, and the supposed absence of evidence for the evolution of life from a common ancestor have taken another blow with the publication of compelling new research that refutes these basic creationist dogmas.
An open access
paper published in Science Advances describes a candidate ancestral mechanism for establishing bilaterality — symmetry along a central axis — in both bilaterians (animals with bilateral symmetry) and the sea anemone
Nematostella. The study, conducted by four researchers from the Department of Neurosciences and Developmental Biology at the University of Vienna, provides crucial insights into the deep evolutionary origins of body plan organisation.
It is also clear from both the paper and the researchers' explanation in a
University of Vienna press release that they regard the Theory of Evolution as essential to interpreting their findings. Their discovery fits squarely within the evolutionary framework and aligns with the established timeline for the diversification of animal life from a common ancestor.
What Is Bilateral Symmetry?
Bilateral symmetry is a body plan in which an organism can be divided into roughly mirror-image halves along a single plane—from head to tail. Most animals, including humans, insects, and vertebrates, display this type of symmetry.
Why Is It Evolutionarily Significant?
- Directional Movement: Bilateral symmetry enables streamlined, forward-facing movement—ideal for seeking food, mates, and avoiding danger.
- Cephalisation: This symmetry is often associated with the development of a head region where sensory organs and the brain concentrate—an evolutionary advantage for processing information efficiently.
- Complexity and Specialisation: It allowed for greater internal organisation and the evolution of specialised body systems (e.g., digestive, nervous, and circulatory).
Evolutionary Milestone
Bilateral symmetry is thought to have evolved over 600 million years ago in a common ancestor of all bilaterians. This innovation marked a major turning point in the history of life, leading to the vast diversity of animal forms we see today.
Bodybuilding in Ancient Times: How the Sea Anemone Got Its Back
New insights into the evolution of the back-belly-axis.
A new study from the University of Vienna reveals that sea anemones use a molecular mechanism known from bilaterian animals to form their back-to-belly body axis. This mechanism ("BMP shuttling") enables cells to organize themselves during development by interpreting signaling gradients. The findings, published in Science Advances, suggest that this system evolved much earlier than previously assumed and was already present in the common ancestor of cnidarians and bilaterians.
Most animals exhibit bilateral symmetry—a body plan with a head and tail, a back and belly, and left and right sides. This body organization characterizes the vast group known as Bilateria, which includes animals as diverse as vertebrates, insects, molluscs and worms. In contrast, cnidarians, such as jellyfish and sea anemones, are traditionally described as radially symmetric, and indeed jellyfish are. However, the situation is different is the sea anemones: despite superficial radiality, they are bilaterally symmetric – first at the level of gene expression in the embryo and later also anatomically as adults. This raises a fundamental evolutionary question: did bilateral symmetry arise in the common ancestor of Bilateria and Cnidaria, or did it evolve independently in multiple animal lineages? Researchers at the University of Vienna have addressed this question by investigating whether a key developmental mechanism called BMP shuttling is already present in cnidarians.
Shuttling for development
In bilaterian animals, the back-to-belly axis is patterned by a signaling system involving Bone Morphogenetic Proteins (BMPs) and their inhibitor Chordin. BMPs act as molecular messengers, telling embryonic cells where they are and what kind of tissue they should become. In bilaterian embryos, Chordin binds BMPs and blocks their activity in a process called "local Inhibition". At the same time, in some but not all bilaterian embryonic models, Chordin can also transport bound BMPs to other regions in the embryo, where they are released again – a mechanism known as "BMP shuttling". Animals as evolutionary distant as sea urchins, flies and frogs use BMP shuttling, however, until now it was unclear whether they all evolved shuttling independently or inherited it from their last common ancestor some 600 million years ago. Both, local inhibition and BMP shuttling, create a gradient of BMP activity across the embryo. Cells in the early embryo detect this gradient and adopt different fates depending on BMP levels. For example, in vertebrates, the central nervous system forms where BMP signaling is lowest, kidneys will develop at intermediate BMP signaling levels, and the skin of the belly will form in the area of maximum BMP signaling. This way, the body's layout from back to belly is established. To find out whether BMP shuttling by Chordin represents an ancestral mechanism for patterning the back to belly axis, the researchers had to look at bilaterally symmetric animals outside Bilateria – the sea anemones.
An Ancient Blueprint
To test whether sea anemones use Chordin as a local inhibitor or as a shuttle, the researchers first blocked Chordin production in the embryos of the model sea anemone Nematostella vectensis. In Nematostella, unlike in Bilateria, BMP signaling requires the presence of Chordin, so, without Chordin, BMP signaling ceased and the formation of the second body axis failed. Chordin was then reintroduced into a small part of the embryo to see if it could restore axis formation. BMP signaling resumed—but it was unclear whether this was because Chordin simply blocked BMPs locally, allowing a gradient to form from existing BMP sources, or because it actively transported BMPs to distant parts of the embryo, shaping the gradient more directly. To answer this, two versions of Chordin were tested—one membrane-bound and immobile, the other diffusible. If Chordin acted as a local inhibitor, both, the immobile and the diffusible Chordin would restore BMP signaling on the side of the embryo opposite to the Chordin producing cells. However, only diffusible Chordin can act as a BMP shuttle. The results were clear: Only the diffusible form was able to restore BMP signaling at a distance from its source, demonstrating that Chordin acts as a BMP shuttle in sea anemones—just as it does in flies and frogs.
A shared strategy across over 600 million years of evolution?
The presence of BMP shuttling in both cnidarians and bilaterians suggests that this molecular mechanism predates their evolutionary divergence some 600-700 million years ago.
Not all Bilateria use Chordin-mediated BMP shuttling, for example, frogs do, but fish don't, however, shuttling seems to pop up over and over again in very distantly related animals making it a good candidate for an ancestral patterning mechanism. The fact that not only bilaterians but also sea anemones use shuttling to shape their body axes, tells us that this mechanism is incredibly ancient. It opens up exciting possibilities for rethinking how body plans evolved in early animals.
Dr. David Mörsdorf, first author
Department of Neurosciences and Developmental Biology
University of Vienna, Vienna, Austria.
We might never be able to exclude the possibility that bilaterians and bilaterally symmetric cnidarians evolved their bilateral body plans independently. However, if the last common ancestor of Cnidaria and Bilateria was a bilaterally symmetric animal, chances are that it used Chordin to shuttle BMPs to make its back-to-belly axis. Our new study showed that.
Grigory Genikhovich, senior author.
Department of Neurosciences and Developmental Biology
University of Vienna, Vienna, Austria
Abstract
Bone morphogenetic protein (BMP) signaling patterns secondary body axes throughout Bilateria and in the bilaterally symmetric corals and sea anemones. Chordin-mediated “shuttling” of BMP ligands is responsible for the BMP signaling gradient formation in many bilaterians and, possibly, also in the sea anemone Nematostella, making BMP shuttling a candidate ancestral mechanism for generating bilaterality. However, Nematostella Chordin might be a local inhibitor of BMP rather than a shuttle. To choose between these options, we tested whether extracellular mobility of Chordin, a hallmark of shuttling but dispensable for local inhibition, is required for patterning in Nematostella. By generating localized Chordin sources in the Chordin morphant background, we showed that mobile Chordin is necessary and sufficient to establish a peak of BMP signaling opposite to Chordin source. These results provide evidence for BMP shuttling in a bilaterally symmetric cnidarian and suggest that BMP shuttling may have been functional in the potentially bilaterally symmetric cnidarian-bilaterian ancestor.
INTRODUCTION
Bone morphogenetic protein (BMP) signaling acts in secondary body axis patterning across Bilateria, and its functions as morphogen have been studied in diverse animal species (1, 2). The mechanisms of the BMP-dependent axial patterning are similar between arthropods and vertebrates, indicative of the shared origin of the secondary, dorsoventral axis in protostome and deuterostome Bilateria, a notion strengthened once broader phylogenetic sampling became available (2–7). Intriguingly, the same mechanisms appear to regulate the secondary axis patterning in the bilaterally symmetric cnidarian Nematostella vectensis, indicating that a BMP-dependent secondary body axis may have evolved before the evolutionary split of Cnidaria and Bilateria [(8, 9), reviewed in (1, 10)]. However, a scenario in which BMP-mediated secondary axes evolved convergently in Bilateria and bilaterally symmetric Cnidaria is also possible (2).
BMPs are secreted signaling proteins of the transforming growth factor–β superfamily frequently acting as heterodimers (11–13). Signaling through the BMP receptor complex (Fig. 1A) results in phosphorylation and nuclear accumulation of the transcriptional effector SMAD1/5, which regulates the expression of many crucial developmental transcription factors and signaling pathway components [(14–18), reviewed in (19, 20)]. BMP signaling is tightly controlled by a plethora of intracellular (14, 21) and extracellular regulators (22–29) of which Chordin (= short gastrulation in insects) is, arguably, the most famous one. Like many other secreted BMP antagonists, Chordin binds BMP ligands, blocks the interaction with their receptor, and thereby inhibits BMP signaling (30). However, Chordin can also have pro-BMP effects and promotes long-range activation of BMP signaling in Drosophila, Xenopus, sea urchins, and in the sea anemone Nematostella (7, 31–34). The phylogenetic distribution of Chordin and two central BMP ligands, BMP2/4 and BMP5-8, and their importance for the secondary axis patterning across phyla suggests that, during early animal evolution, these molecules may have represented the minimum requirement for the formation of the bilaterally symmetric body plan (2, 10). However, to evaluate such a possibility, we need to understand the “mode of action” of BMPs and Chordin outside Bilateria, and our model, the sea anemone Nematostella, allows exactly that.
Fig. 1. Possible modes of action of BMP signaling during axial patterning in Nematostella.
(A) BMP signaling pathway. BMP dimers bind the heterotetrameric receptor complex, resulting in the phosphorylation of SMAD1/5. pSMAD1/5 forms a complex with the Co-Smad SMAD4, which regulates transcription in the nucleus. Chordin binds BMPs preventing them from activating the receptor complex. Metalloproteases like Tolloid and BMP-1 cleave Chordin and release BMP ligands from the inhibitory complex in Bilateria. (B) Expression domains of BMPs and BMP antagonists in an early Nematostella larva. Oral view corresponds to the optical section indicated with grey dashed line on the lateral view. Pink circles show the nuclear pSMAD1/5 gradient. (C) The shuttling model suggests that in Nematostella, a mobile BMP-Chordin complex transports BMPs through the embryo. Receptor binding is inhibited in cells close to the Chordin source due to high concentrations of Chordin. On the opposite side of the directive axis, BMPs bind their receptors and activate signaling upon release from Chordin. Tolloid might be involved in the cleavage of Chordin and release of BMPs from the complex with Chordin also in Nematostella. (D) In the local inhibition model, Nematostella Chordin acts locally to inhibit BMP signaling and promote the production of BMP2/4 and BMP5-8 mRNA. Chordin mobility is not required for asymmetric BMP signaling.
BMP signaling in Nematostella becomes detectable during early gastrula stage in a radially symmetric domain: The phosphorylated form of the BMP signaling effector SMAD1/5 (pSMAD1/5) is detected in the nuclei around the blastopore (14, 35). Shortly after the onset of BMP activity, the radial symmetry of the embryo breaks, establishing the secondary, “directive” body axis with minimum BMP signaling intensity detectable on the side of BMP2/4, BMP5-8, and Chordin expression and maximum BMP signaling on the side opposite to it (Fig. 1B) (14, 34, 35). The symmetry break occurs despite the fact that mRNAs of the type I BMP receptors Alk2 and Alk3/6 and the type II receptor BMPRII are maternally deposited (36) and remain weakly and ubiquitously expressed in the embryo (fig. S1) gradually developing a slight bias toward the “high pSMAD1/5” side of the directive axis by early planula stage (14). BMP2/4 and BMP5-8 are co-expressed in the late gastrula/early planula, and both these ligands are crucial for BMP signaling and directive axis patterning because knockdown of either ligand abolishes pSMAD1/5 immunoreactivity and completely radializes the embryo (34). Individual knockdowns of either BMP2/4 or BMP5-8 result in a strong up-regulation of transcription of both BMP2/4 and BMP5-8 in a radially symmetric domain showing that both these genes are negatively controlled by BMP signaling. Despite transcriptional up-regulation of BMP2/4 in BMP5-8 morphants and BMP5-8 in the BMP2/4 morphants, no nuclear pSMAD1/5 is observed in such embryos (9, 34, 35), suggesting that BMP2/4 and BMP5-8 signal as an obligate heterodimer during axial patterning in Nematostella.
The “core” BMPs, BMP2/4 and BMP5-8, are not the only BMP ligands present in the embryo at this stage. GDF5-like (GDF5L) is a BMP ligand expressed on the side of strong BMP signaling (Fig. 1B). GDF5L expression is abolished in the absence of BMP2/4 and BMP5-8, and the role of GDF5L appears to be in steepening the pSMAD1/5 gradient making it a “modulator” BMP (14, 34, 37). The BMP signaling gradient is stable over many (>24) hours during which it patterns the directive axis (9, 14, 34, 35, 37). Considering the short half-life of phosphorylated SMAD1/5 reported in other systems (15, 21), this indicates that long-range transport (~100 μm) of BMP2/4 and BMP5-8 and constant receptor complex activation is necessary to maintain BMP signaling. How it exactly happens that the core BMP ligands, BMP2/4 and BMP5-8, are expressed on one side of the embryo and the peak of BMP signaling activity is on the opposite side is currently unknown.
One possible explanation involves Chordin-mediated shuttling of BMP ligands, described in the dorsoventral patterning in Drosophila and Xenopus (7, 34, 38). In this model, Chordin inhibits BMP function locally, close to the Chordin source cells, but promotes long-range BMP signaling by forming a mobile complex with the BMP dimer, which is released once Chordin is cleaved by the metalloprotease Tolloid. The probability that this BMP dimer will bind its receptors rather than another, yet uncleaved Chordin increases with the distance to the Chordin source (Fig. 1C). In Nematostella, the shuttling model was proposed when we found that, unlike in all bilaterian models studied thus far, depletion of Chordin results in the loss of BMP signaling rather than in its enhancement (34). However, given that, in Nematostella, BMP signaling indirectly represses the transcription of the core BMPs, BMP2/4 and BMP5-8, and activates the transcription of the modulator BMP, GDF5-like (14), an alternative explanation is also possible: In this “local inhibition” scenario, Chordin locally represses BMP signaling enabling BMP2/4 and BMP5-8 production. BMP2/4 and BMP5-8 diffuse into the area of low or no Chordin (i.e., to the GDF5-like side of the directive axis) and bind the receptors there. In this scenario, Chordin knockdown results in a transient de-repression of the BMP2/4/BMP5-8–mediated signaling, which, in turn, leads to the repression of the BMP2/4 and BMP5-8 transcription. Because, in the absence of BMP2/4 and BMP5-8, GDF5-like expression is also lost (9), we may end in a situation when no BMP ligands are produced and no BMP signaling takes place, as it is the case in the Chordin morphant (9, 34). This local inhibition model, in which Chordin acts exclusively as a local repressor of BMP signaling (Fig. 1D), is similar to the situation in zebrafish, where extracellular mobility of Chordin is not required (39–41). Here, we address the role of Chordin in the BMP-dependent axial patterning in the sea anemone Nematostella and test these two alternative models.
This discovery poses a significant problem for creationist claims because it provides clear molecular and developmental evidence for a shared evolutionary origin between animals with bilateral symmetry and simpler organisms like sea anemones, which lack such symmetry as adults. The fact that the genetic and developmental mechanisms for establishing a "back" or body axis predate the emergence of bilaterally symmetrical animals suggests that these features evolved gradually through modification of existing biological systems—not through sudden, miraculous creation.
Creationism relies on the assertion that complex body plans appeared abruptly, fully formed, and without evolutionary precursors. However, the findings in this study directly contradict that idea. They show that the genetic toolkit required for bilateral body structures was already present in the common ancestor of cnidarians (like sea anemones) and bilaterians and was likely repurposed and elaborated upon over millions of years. This is exactly what evolutionary theory predicts.
Moreover, the study aligns neatly with the established evolutionary timeline based on genetics, developmental biology, and the fossil record. There is no need to invoke supernatural causes or to assume that animals were created independently and without shared ancestry. Instead, the evidence points to deep continuity in the genetic architecture of life—a hallmark of common descent and a major blow to the isolated, one-off acts of creation claimed by young-Earth and Intelligent Design creationists alike.
