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First published online June 8, 2006
doi: 10.1242/10.1242/dev.02425
Meeting Review |
Max-Planck Institute for Developmental Biology, Department for Evolutionary Biology, Tübingen, D-72076, Germany. e-mail: ralf.sommer{at}tuebingen.mpg.de
The 2006 symposium of the RIKEN Center for Developmental Biology in Kobe, Japan, was entitled `Logic of development: new strategies and concepts'. The purpose of the meeting was to uncover how our understanding of the logic of developmental processes is changing in the light of novel techniques and strategies. The speakers provided a comprehensive overview of diverse topics, such as the power of functional genomics and imaging approaches, and the phenomenon of non-coding RNAs and their role in development. A wide range of processes and mechanisms at the molecular, cellular and organismic level were presented, as were many novel concepts and strategies, which together highlighted the importance of interdisciplinary approaches.
Introduction
The fundamental questions of developmental biology still capture our fascination: how is the single-cell egg transformed into the beautiful adult organism, whether it be a bird, fly, worm or plant; and how are the diverse cell types and tissues generated in a context-dependent manner (see Fig. 1)? However, in modern developmental biology, with its heavy dependence on technology, novel research strategies can change our understanding of processes and mechanisms dramatically. The 2006 symposium of the RIKEN Center for Developmental Biology (CDB), which was organized by Masatoshi Takeichi, Asako Sugimoto, Hiroki R. Ueda and Shigeo Hayashi (CDB, Kobe, Japan), and Steve Cohen (European Molecular Biology Laboratory, Heidelberg, Germany) covered many areas of developmental biology and searched for novel strategies and concepts. In this meeting review, I highlight some of the many outstanding contributions of this very successful and broad meeting.
Small RNAs
One central topic of the meeting was the function of microRNAs (miRNAs) and
other small RNAs in gene regulation and development, which was covered in
three sessions. With speakers from both the animal and plant fields,
similarities and differences in miRNA function were illustrated and the
changing thoughts about miRNA function were put into a historical perspective.
In animals, miRNAs show imprecise pairing and mismatch with their target
messenger RNAs (mRNAs). Victor Ambros (Dartmouth Medical School, Hanover, NH,
USA) pointed out the important concept that the mismatch between the miRNA and
its target mRNAs provides an opportunity for different mechanisms of gene
regulation. Basically, three distinct network modes can be distinguished
(Fig. 2). First, several miRNAs
can converge on the regulation of the same downstream target
(Fig. 2A). Alternatively, a
single miRNA can regulate independent target genes, providing a divergent
rather than a convergent principle (Fig.
2B). And finally, miRNAs can target genes in a linear one-to-one
fashion (Fig. 2C). René
Ketting (Hubrecht Laboratory, Utrecht, The Netherlands), Eric Miska (The
Wellcome Trust/Cancer Research UK Gurdon Institute, Cambridge, UK) and Steve
Cohen provided multiple examples of miRNA function in animal development from
worms, flies and vertebrates. Haruhiko Siomi (University of Tokushima,
Tokushima, Japan) demonstrated the function of the Argonaute protein Ago2 in
the Drosophila RNAi pathway. In the final talk of the miRNA sessions,
Cohen provided some useful numbers from his studies in Drosophila to
exemplify the importance of small RNAs in the development and homeostasis of
animals: Drosophila contains at least 55 well-characterized miRNAs
(this number should increase over time), each of which has around 100 target
genes. This adds up to more than 5500 target sites in 
3600 genes that are
regulated by miRNAs, which themselves account for 30% of the predicted
Drosophila genes. Two aspects of miRNA function in animals are of
general importance. First, regulation by miRNAs is commonly seen in
developmental control genes, whereas genes involved in protein biosynthesis,
RNA metabolism, DNA repair, RNA splicing and other `housekeeping' functions
are avoided in a statistically significant manner. Second, miRNAs are
components that increase the temporal and spatial precision of regulatory
processes and increase the robustness of development
(Stark et al., 2005
). This
function of miRNAs is unlike that of transcription factors, which make
developmental decisions and often work as developmental switches.
The current understanding of miRNA function reveals important differences
in their function between plants and animals. Detlef Weigel (Max-Planck
Institute for Developmental Biology, Tübingen, Germany) summarized
several of these differences and provided an overview of the numbers of miRNAs
and target genes in Arabidopsis thaliana. There are more than 200
confirmed miRNAs in plants, which fall into some 30 families. These families
have conserved target sites, often in transcription factors genes. In contrast
to animals, miRNA target motifs in plants are mostly in the coding sequence of
their respective target. Most importantly, miRNAs in plants seem to have a
narrow specificity, in contrast to the broad specificity of animal miRNAs
(Schwab et al., 2005). One
explanation for this important difference could be that miRNAs evolved
independently in plants and animals, a hypothesis that remains to be tested.
Taken together, the first observations of homology-mediated silencing
mechanisms in plants and worms, which occurred a little more than a decade ago
have meanwhile turned into an independent research branch on small non-coding
RNA pathways (Pasquinelli,
2006). One aspect that all miRNA speakers agreed upon is that many
important insights are to be expected from further studies on miRNA function
and regulation.
Functional genomics
The second important topic of the meeting was functional genomics. John Hogenesch (The Scripps Research Institute, Jupiter, FL, USA) introduced cell-based screening approaches and their usefulness in the annotation of the mammalian genome. He demonstrated that when used with a powerful bioassay, cell-based screening approaches are able to reveal important functions for components of signaling systems and non-coding RNAs in a similar way. Nicolas Bertin from Marc Vidal's laboratory (Harvard Medical School, Boston, MA, USA) described the initial steps towards an objective, systematic, in vivo spatiotemporal localization of expression in C. elegans. This new biological map, the localizome, could be used to refine the current static protein-protein interaction map and also to gain a system-level understanding of gene regulation during the post-embryonic development of C. elegans.
|
). Such
large-scale functional descriptions can profit tremendously from computational
technologies that enable quantitative analyses. Shuichi Onami (Keio
University, Yokohama, Japan) showed his very powerful strategies to quantify
structures and features in the C. elegans embryo. Using
high-resolution image processing and computer simulation, the phenotypic
analysis of gene knockdowns by RNAi becomes possible in an automated
manner. Finally, Duncan Davidson (MRC Human Genetics Unit, Edinburgh, UK) introduced the audience to the mouse expression pattern database. Given the complexity of the mammalian genome and, more importantly, the complexity of the developing embryo with its three-dimensional structures, highly sophisticated computational tools are necessary to generate information that seems more straightforward in worms and flies. The functional genomics sessions covered a diverse array of topics, but they had in common that the application of computational approaches to experimental studies represents a key research strategy in modern developmental biology.
Systems biology and live-cell imaging
In the past 5 years, functional genomics and miRNAs have changed the
strategies and concepts in developmental biology tremendously. However,
additional approaches for studying developmental processes are coming of age,
two of which were given separate sessions at the meeting. Systems biology was
introduced by two speakers, who illustrated well the different ideas and
approaches of systems biology. Ron Weiss (Princeton University, Princeton, NJ,
USA) introduced pattern formation in synthetic biology. He highlighted how
multi-cellular systems can be synthetically generated by engineering and that
such systems will help us to understand the quantitative aspects of cell-cell
communication and pattern formation in natural systems. From a completely
different angle, Hiroki R. Ueda (RIKEN CDB, Kobe, Japan) summarized his
studies on the analysis and synthesis of biological networks. Using the
mammalian circadian clock as a case study, he described how the combination of
bench work - studying the regulatory circuits of transcription factors - and
modeling studies can help to elucidate a comprehensive understanding of
circadian systems (Ueda et al.,
2005). As with the functional genomics studies, Ueda's work shows
the importance of combining experimental and computational studies.
|
). At this point, the participants of the meeting finally
became aware of how important high-resolution and high-speed imaging systems
are for the understanding developmental mechanisms. Conclusions
Taken together, the CDB 2006 symposium on the logic of development covered a wide area of developmental biology and demonstrated, in an exciting way, the power of modern approaches for studying developmental systems. As pointed out by Steve Cohen in his closing remarks of the meeting, one of the most exciting insights to be gained from this meeting is the enormous potential that is inherent in combining experimental and computational approaches, a strategy that is constantly gaining in importance. In addition, the generation of new data in large-scale functional genomic approaches requires intelligent retrieval strategies to make these data accessible to biologists. The participants of the meeting left Kobe in the optimistic spirit that these long-standing problems of high-throughput approaches - storage, quantification and resolution of data-could be solved.
As usual, there is a `but'. At the same time as computational biology and
large-scale approaches are becoming more important as a research strategy in
the analysis of model organisms, lessons from evolution should not be
forgotten. In the evolutionary session, Detlev Arendt (EMBL, Heidelberg,
Germany) and Kiykazu Agata (Kyoto University, Kyoto, Japan) showed how
different animals with a different body plan are constructed, by describing
their work in the annelid Platynereis dumerilii and in planarians,
respectively. But one does not have to study members of different phyla to
learn about important differences in the regulation and the logic of
development, as shown by recent comparisons in distinct species of nematode,
Pristionchus pacificus and C. elegans
(Zheng et al., 2005).
In conclusion, lessons and concepts from an extraordinarily broad range of biological and developmental research fields have outlined the multitude of inroads into modern developmental biology. To finish with the final words of Victor Ambros: `this was an exciting meeting, helping life's wonders to be rediscovered'.
ACKNOWLEDGMENTS
I thank Drs D. Weigel, N. Bertin, V. Ambros and M. Riebesell for comments on the manuscript, and the participants of the meeting for permission to include their work. I apologize to all those participants whose work I could not refer to owing to space limitations. My laboratory is supported by the Max Planck Society.
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