MEETING REVIEW 2451
Development 133, 2451-2453 (2006) doi:10.1242/dev.02425

Ralf J. Sommer
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 wasto uncover how our understanding of the logic ofdevelopmental processes is changing in the light of novel
techniques and strategies. The speakers provided acomprehensive overview of diverse topics, such as the power offunctional genomics and imaging approaches, and thephenomenon of non-coding RNAs and their role indevelopment. A wide range of processes and mechanisms at themolecular, cellular and organismic level were presented, aswere 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 thebeautiful adult organism, whether it be a bird, fly, worm or plant; andhow are the diverse cell types and tissues generated in a contextdependent manner (see Fig. 1)? However, in modern developmentalbiology, with its heavy dependence on technology, novel researchstrategies can change our understanding of processes andmechanisms 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 (EuropeanMolecular Biology Laboratory, Heidelberg, Germany) covered
many areas of developmental biology and searched for novel
strategies and concepts. In this meeting review, I highlight some ofthe many outstanding contributions of this very successful and broadmeeting.
Small RNAs
One central topic of the meeting was the function of microRNAs(miRNAs) and other small RNAs in gene regulation anddevelopment, which was covered in three sessions. With speakers
from both the animal and plant fields, similarities and differences inmiRNA 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 MedicalSchool, Hanover, NH, USA) pointed out the important concept thatthe 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 samedownstream target (Fig. 2A). Alternatively, a single miRNA canregulate independent target genes, providing a divergent rather thana convergent principle (Fig. 2B). And finally, miRNAs can target
genes in a linear one-to-one fashion (Fig. 2C). René Ketting
Max-Planck Institute for Developmental Biology, Department for EvolutionaryBiology, Tübingen, D-72076, Germany.
e-mail: ralf.sommer@tuebingen.mpg.de(Hubrecht Laboratory, Utrecht, The Netherlands), Eric Miska (TheWellcome 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 theDrosophila 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 andhomeostasis of animals: Drosophila contains at least 55 wellcharacterized miRNAs (this number should increase over time),each of which has around 100 target genes. This adds up to morethan 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 generalimportance. First, regulation by miRNAs is commonly seen indevelopmental control genes, whereas genes involved in protein
biosynthesis, RNA metabolism, DNA repair, RNA splicing andother ‘housekeeping’ functions are avoided in a statisticallysignificant manner. Second, miRNAs are components that increase
the temporal and spatial precision of regulatory processes andincrease the robustness of development (Stark et al., 2005). Thisfunction of miRNAs is unlike that of transcription factors, whichmake developmental decisions and often work as developmental
switches.
The current understanding of miRNA function reveals importantdifferences in their function between plants and animals. Detlef
Weigel (Max-Planck Institute for Developmental Biology,
Tübingen, Germany) summarized several of these differences andprovided 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. Incontrast to animals, miRNA target motifs in plants are mostly in thecoding sequence of their respective target. Most importantly,
miRNAs in plants seem to have a narrow specificity, in contrast tothe 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 thatremains to be tested. Taken together, the first observations ofhomology-mediated silencing mechanisms in plants and worms,
which occurred a little more than a decade ago have meanwhileturned 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 theirusefulness 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 forcomponents of signaling systems and non-coding RNAs in a similarway. Nicolas Bertin from Marc Vidal’s laboratory (Harvard MedicalSchool, Boston, MA, USA) described the initial steps towards anobjective, systematic, in vivo spatiotemporal localization ofexpression in C. elegans. This new biological map, the localizome,DEVELOPMENT

New inroads to development

2452 MEETING REVIEWDevelopment 133 ()A Convergent

B Divergent

miRW
miRX
miRY

C LinearTarget B
Target A

miRZ

Target C

miRV

Target E

Target DFig. 2. Network modes for different mechanisms of gene
regulation by miRNAs. (A-C) Several miRNAs can converge on theregulation of the same downstream target, a single miRNA can diverge
to regulate independent target genes and, ﬁnally, miRNAs can target
genes in a linear fashion.

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.
Asako Sugimoto (RIKEN CDB, Kobe, Japan) described her work
towards generating a detailed ‘developmental phenome’ of C.
elegans. Using RNAi approaches, her laboratory is providing asystematic phenotypic description of gene knockouts during
embryonic and post-embryonic development (Sugimoto, 2004).
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 andcomputer 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 embryowith its three-dimensional structures, highly sophisticatedcomputational 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 incommon that the application of computational approaches toexperimental 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 twospeakers, who illustrated well the different ideas and approaches ofsystems biology. Ron Weiss (Princeton University, Princeton, NJ,USA) introduced pattern formation in synthetic biology. He
highlighted how multi-cellular systems can be syntheticallygenerated by engineering and that such systems will help us toConclusions
Taken together, the CDB 2006 symposium on the logic ofdevelopment covered a wide area of developmental biology anddemonstrated, in an exciting way, the power of modern approaches
for studying developmental systems. As pointed out by Steve Cohenin his closing remarks of the meeting, one of the most exciting
insights to be gained from this meeting is the enormous potentialthat 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 makethese data accessible to biologists. The participants of the meetingleft Kobe in the optimistic spirit that these long-standing problemsof high-throughput approaches – storage, quantification andresolution 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 asa research strategy in the analysis of model organisms, lessons fromevolution should not be forgotten. In the evolutionary session, Detlev
Arendt (EMBL, Heidelberg, Germany) and Kiykazu Agata (KyotoUniversity, Kyoto, Japan) showed how different animals with aDEVELOPMENTFig. 1. The painting ‘Clairvoyance’ by Rene Magritte (1936) was theofficial poster of the symposium ‘Logic of development: new strategies
and concepts’. Copyright VG Bild-Kunst, 2006.

understand the quantitative aspects of cell-cell communication andpattern formation in natural systems. From a completely different
angle, Hiroki R. Ueda (RIKEN CDB, Kobe, Japan) summarized hisstudies on the analysis and synthesis of biological networks. Using
the mammalian circadian clock as a case study, he described how thecombination of bench work – studying the regulatory circuits oftranscription factors – and modeling studies can help to elucidate acomprehensive understanding of circadian systems (Ueda et al.,2005). As with the functional genomics studies, Ueda’s work shows
the importance of combining experimental and computationalstudies.
Atsushi Miyawaki (RIKEN Brain Science Institute, Wako, Japan)
introduced the audience to the spatial and temporal patterning ofsignaling processes in the brain. He demonstrated how thecombination of GFP-related imaging systems with fluorescencecross-correlation spectroscopy (FCCS) and the use of novel
fluorescent probes provides new solutions for understanding thetemporal, as well as the spatial, patterns of signaling systems.
Yasushi Okada (The University of Tokyo, Japan) used high-speed
live imaging techniques to study nodal flow and its function duringleft-right axis specification in mice. He introduced a hydrodynamic
mechanism and employed wonderful fluorescent recordings ofsurface lipids to visualize the directed transport of particles thatmight trigger the final developmental decisions during left-right axisspecification (Okada et al., 2005). At this point, the participants ofthe meeting finally became aware of how important high-resolution
and high-speed imaging systems are for the understanding
developmental mechanisms.

different body plan are constructed, by describing their work in theannelid 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. Tofinish with the final words of Victor Ambros: ‘this was an exciting
meeting, helping life’s wonders to be rediscovered’.
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 toowing to space limitations. My laboratory is supported by the Max PlanckSociety.

MEETING REVIEW 2453
References
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Mechanism of nodal ﬂow: a conserved symmetry breaking event in left-right axis
determination. Cell 121, 633-644.
Pasquinelli, A. E. (2006). Demystifying small RNA pathways. Dev. Cell 10, 419424.
Schwab, R., Palatnik, J. F., Riester, M., Schommer, C., Schmid, M. andWeigel, D. (2005). Speciﬁc effects of microRNAs on the plant transcriptome.
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Stark, A., Brennecke, J., Bushati, N., Russell, R. B. and Cohen, S. M. (2005).
Animal microRNAs confer robustness to gene expression and have signiﬁcant
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Sugimoto, A. (2004). High-throughput RNAi in Caenorhabditis elegans: genomewide screens and functional genomics. Differentiation 72, 81-91.
Ueda, H. R., Hayashi, S., Chen, W., Sano, M., Machida, M., Shigeyoshi, Y.,
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Development 133 ()