Fischer, A. H. L. and J. Smith (2012). “Evo-Devo in the Era of Gene Regulatory Networks.” Integrative and Comparative Biology.

Have you ever tried to understand clockwork? How would you go about trying to figure it out? One way would be to carefully observe the clockwork for a certain period of time to see how all the cogs and springs, enclaspments and wheel trains move together. After that you could interfere with individual parts to see how the perturbation of one affects all other movements.The development of organisms from fertilized eggs to adult bodies with many cell types surpasses even the complexity of clockwork. However, as in clocks where numerous pinions interact to keep precise time, in an organism numerous genes act together in gene regulatory networksto ensure correct gene expression. Understanding the gene regulatory network is the ultimate way to a deep and mechanistic understanding of animal development.

The “clockwork” we are trying to understand is the developmental gene regulatory network of the sea anemone Nematostella vectensis. The first steps are, as with the clockwork analogy, careful observation. To this end we analyzed numerous developmental stages of the sea anemone by quantitative RNAseq. RNAseq is a new sequencing technology that allows analyzing and quantifying billions of sequences at the same time and thus allows deep insights into developmental processes.

For the next step, we are currently using different drugs that affect important developmental proteins and analyzing the effect on all other developmental genes by real time PCR and quantitative RNAseq. This is like blocking one cog in the clockwork to see which cogs keep moving despite the interference and which cogs stop running. In this way, we will understand more about the logic behind the clockwork – that is the roles each gene plays during development.

However, we consider this just the beginning. To understand the evolution of gene regulatory networks in animals our goal is to apply these methods to many animals. The sea anemone is an ideal starting point due to its strategic phylogenetic position as one of our most distant cousins. Different molecular techniques are already established and it is easy to keep in culture in the laboratory. More importantly, Nematostella is a very simple organism – a Cnidarian – a group of simple animals that also includes corals and sea jellies. The simple body plan of Nematostella makes it exceptionally interesting as a model, in comparison with more elaborate body plans of animals such as fly, frog and even humans. The last common ancestor of Nematostella and fly, frog and humans lived around 600 Million years ago and since then, many characteristics have changed. It is not always easy to find out, what is there because of evolutionary inheritance and what are evolutionary novelties. However, by comparing the gene regulatory network and identifying similarities between the gene interactions in the sea anemone and those networks in humans, frogs and flies, we are able to reconstruct how genes interacted in the past. This will allow us to understand which gene interactions are of particular importance and which points in the network can be altered. It is like reconstructing the first clock mechanisms – and ultimately it will take our understanding of gene regulation in animals to a new level to dissect this original clockwork.