Meeting Review Genomics and Development: Taking Developmental Biology to New Heights

Franc¸ois Spitz and Eileen E.M. Furlong*Developmental Biology ProgrammeEMBLHeidelberg 69117GermanyThe 2006 Arolla meeting brought together scientistsfrom around the globe to discuss how genomic scaleanalyses can enhance progress in understandingdevelopmental biology.The Arolla meetings began in 1972 and have been heldevery three years ever since. The meetings have a longtradition of being very interactive and their fabulouslocation, nestled within the peaks and glaciers of theSwiss Alps, helps to promote constructive discussion.This year’s meeting, ‘‘Genomics of Development,’’ wasorganizedbyDenisDuboule(UniversityofGeneva,Swit-zerland), Ivan Rodriguez (University of Geneva), andCynthia Kenyon (UCSF, USA) and sponsored by boththe European Molecular Biology Organization (EMBO)and the Swiss National Science Foundation (SNF)through the National Centre of Competence in Research‘‘Frontiers in Genetics.’’The past five years have seen the release of the se-quenced genomes of some of the major model organ-isms used in developmental biology and of an ever in-creasing number of genomic technologies, which allowthe study of a gene’s expression, regulation, and func-tion at the level of the entire genome. By bringing to-gether people who are using new genomic strategiesor emerging model organisms, the Arolla meeting‘‘Genomics of Development’’ aimed to assess how thisfusion of genomics and developmental biology will pos-sibly change our conceptual understanding of develop-mental processes. This meeting report highlights par-ticularly nice examples in which ‘‘new approaches’’ toaddress ‘‘old questions’’ have been successfully usedto increase our understanding of development andevolution.Fusing Functional Genomics with Development:Large-Scale Functional Genomics Screens —Characterizing New Gene FunctionEven for very well-studied model organisms, the func-tion of the vast majority of genes remains uncharacter-ized. One of the properties shared by large-scale geno-mic approaches and traditional forward genetic screensis the unbiased exploration of gene function. Three talkshighlighted how large-scale genetic screens can be ex-tended, from flies and worms, to mice.Oneoftheadvantagesofchemicalmutagens,suchasEMS and ENU, is their ability to induce different typesof point mutations within the same locus, resulting ina spectrum of phenotypes that tend to more accuratelymodel human diseases. A nice example was presentedby Steve Brown (Harwell, UK), who described a largescreen of 30,000 ENU mutant mice for dominant muta-tions affecting auditory and vestibular function, whichidentified 82 loci resulting in hearing defects. One suchmutation, Junbo, causes chronic middle ear inflamma-tory disease that is clinically very similar to the chronicotitis media in children. Surprisingly, Junbo maps tothe well-studied zinc finger transcription factor Evi1.Finding a novel function for Evi1 in audition highlightsthe strength of phenotype-driven, large-scale mutagen-esis as well as the need for a precise assessment of thephenotypes of available mutants animals. For the latter,the specialized phenotyping platforms of the ‘‘mouseclinics’’(MartinHrabe´ deAngelis,GSF,Germany)shouldbe very instrumental.Similar to EMS/ENU screens, RNAi gene knockdowntypically gives a range of phenotypes, which effectivelyrepresent a hypomorphic series. Nick Van Hateren (Uni-versity of Sheffield, UK) and coworkers made use of thisapproachtolookfortheroleofcadheringenesinthefor-mation of the chicken neural tube. They systematicallyknocked down the 41 genes with Cadherin motifs thatare expressed in the neural tube by a plasmid-basedRNAi system (Das et al., 2006) and observed specificphenotypes including altered size and morphology,premature differentiation, and migration defects. Thisstudy, which can be scaled-up, offers great potentialto decipher gene functions and the genetic hierarchycontrolling neural tube formation.ArealadvantageofRNAiisitsapplicationtomodelor-ganisms where little or no genetic tools are available,providing a way to complement many years of beautifulembryology with functional assays. Of note on this topicwas a talk from Brigitte Galliot (University of Geneva,Switzerland). Her group developed an efficient methodto silence gene expression through dsRNA feeding inhydra (Figure 1A). The first gene knocked down, aSPINK-related serine protease inhibitor, is involved inthe immediate cytoprotective function provided by thegland cells after amputation (Chera et al., 2006). Amaz-ingly, the autophagy phenotype is similar to what is ob-servedinthemouseexocrinepancreaswhentherelatedgene is mutated. In combination with the developmentof genomic resources for cnidarians (Thomas Holstein,University of Heidelberg, Germany), these powerfultools will help reveal the secrets of developmental plas-ticity and regeneration in hydra.C.elegansis currentlytheonly modelorganism wheregenome-wide RNAi screens can be easily conductedwithin the developing embryo. Thanks to the construc-tion of a library of dsRNA-expressing bacterial strainsmade by Julie Ahringer’s lab (Cambridge, UK), the bac-teria can be conveniently fed to worms to produce ef-ficient gene knockdown (Kamath et al., 2003). JulieAhringer demonstrated the power of this approach ina high throughput RNAi screen to identify genes in-volved in asymmetric cell division and cell polarity.Jasper Mullenders from Rene´ Bernards’ group (Nether-lands Cancer Institute, Amsterdam) showed how similar