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The fresh-water polyp Hydra is famous for its virtually unlimited regenerative capability and hence a perfect model for molecular stem cell and regeneration research.

The fresh-water polyp Hydra, a member of the over 600-million-year-old phylum Cnidaria, is famous for its virtually unlimited regenerative capability and hence a perfect model for molecular stem cell and regeneration research.

Hydra can also help us understand how our body axes came to evolve, as scientists at the Centre for Organismal Studies of Heidelberg University in collaboration with a colleague at the Max F. Perutz Laboratories (MFPL) of the University of Vienna and the Medical University of Vienna show. Their findings have recently been published in the scientific journal “Nature”. In Heidelberg, the researchers under the direction of Thomas Holstein with his colleague Suat Özbek delved into the reproduction process of Hydra at the molecular level. Heiko Schmidt at the Center for Integrative Bioinformatics Vienna at the MFPL supported them with the data analysis.

The Hydra reproduces asexually by producing buds on the body wall of the adult, which then mature to form new polyps. The scientists discovered that this process is controlled by a signal pathway that also triggers the left-right asymmetry of organs in higher animals, including humans. "It is amazing that components of this pathway must have existed already in the common ancestor of Cnidaria and vertebrates 600 million years ago. It supports our earlier findings that the molecular complexity in these ancient animals was much higher than the morphological complexity”, says Heiko Schmidt.

Three body axes
One fundamental question in biology is what constitutes the basic type of the animal body plan and how did all the more complex forms, including humans, evolve from it. At the simplest level, this body plan can be described by three axes – the familiar X, Y and Z axes from geometry. These are the anterior-posterior (AP) axis, which determines the position of the mouth in front and the anus at the rear, the dorsal-ventral (DV) axis, which in vertebrates separates the front of the body from the back, and the left-right (LR) axis, which creates a mirror-like symmetry of our extremities and left-right asymmetry of the organs.

Symmetry break

These three body axes are defined early on in embryonic development. A fertilized egg cell begins to divide, initially producing a ball-shaped entity of undifferentiated cells. It is in this early stage of the embryo that the position of the first opening of the body is determined, which simultaneously defines the AP axis. “This process can be explained geometrically as a symmetry break, and other symmetry breaks follow that define the other two axes, the DV and LR axes,” explains Thomas Holstein.

The genetic basis for each of these body axes had already been identified in the embryonic development of humans, other vertebrates, and even in insects and worms. Evolutionarily highly-conserved molecular signal systems act as molecular vectors to define each of the body axes and control the formation of different cell types. Many of these so-called developmental genes also play a major role in the development of cancer.

In their molecular analyses, the researchers identified what is known as Nodal signaling in the primitive system of the fresh water polyp, which has only one clearly defined body axis with one opening. "Until now, this signal path has only been known in bilaterally symmetric animals [editor’s note: such as worms and vertebrate animals] where it is involved in establishing a signal centre for early embryonic development and left-right asymmetry,” explains first author Hiroshi Watanabe, a member of Thomas Holsteins’s group.

Starting point in the evolution of left-right axis formation
The scientists were able to demonstrate that the Hydra also has a Nodal-type gene, which together with the main target genes of the activated Nodal signal path, is involved in the asymmetrical positioning of the Hydra buds. Thus, the study presents the first evidence of the existence and participation of the Nodal signal pathway in axis induction in a “radially” symmetric organism.

“This may be the starting point in the evolution of left-right axis formation in the bilaterally symmetric animals. Identifying just how this complex bilaterian body plan evolved opens up other exciting areas of research,” explains Holstein. These findings, however, already point to how similar the core molecular-level embryonic processes are between the simple Cnidaria and the vertebrates, including human beings.

Original publication:

Hiroshi Watanabe, Heiko A. Schmidt, Anne Kuhn, Stefanie K. Höger, Yigit Kocagöz, Nico Laumann-Lipp, Suat Özbek & Thomas W. Holstein: “Nodal signalling determines biradial asymmetry in Hydra”. Nature online (24 August 2014), doi:10.1038/nature13666

» Max F. Perutz Laboratories