Objective Early mammalian development is a unique process creating an extraembryonic structure. Despite its importance for understanding mammalian development and direct relevance to clinical practice, the mechanism underlying polarity establishment in the mammalian embryo has long been elusive. One of the major obstacles is the lack of description in molecular terms, since very few genes are known to specify the early lineages. Our recent studies provide a conceptual basis, suggesting that the mechanism is unique to mammals. The primary aim of this proposal is to elucidate the molecular program and the novel principle of early mammalian development at a systems level. To comprehensively identify molecules involved in early mouse development, we will conduct two complementary screens. One is a lentivirus-based promoter-trap screen: Venus-reporter is to be expressed under the endogenous control of the integrated genomic locus, which will be monitored using our live-embryo imaging system. Embryos showing a differential expression pattern will be selected for further analysis. As a complementary approach, single-blastomere-derived cRNAs are generated from embryos of various stages by the recently developed single-cell cRNA amplification method, followed by microarray analysis to statistically identify gene clusters differentially expressed in specific blastomeres. Function of the genes identified in two screens will be examined by RNAi and maternally conditional KO. Finally, the knowledge will be integrated into our computer simulation that successfully reconstitutes blastocyst morphogenesis. In the long term, the obtained tools (markers and Venus-trap lines) will provide a basis for functional siRNA screen. Genetic screen in early mouse embryos has never been achieved. Though we anticipate certain difficulties, we are confident that with the relevant expertise of collaborators and ourselves, these can be resolved and a substantial advance will be made in this important area. Fields of science natural sciencesbiological scienceszoologymammalogymedical and health sciencesclinical medicineembryologynatural sciencesmathematicsapplied mathematicsmathematical model Keywords early mammalian development early mammalian development embryonic patterning live-imaging gene-trap embryonic patterning gene-trap live-imaging Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-SG-LS1 - ERC Starting Grant - Molecular and Structural Biology and Biochemistry Call for proposal ERC-2007-StG See other projects for this call Funding Scheme ERC-SG - ERC Starting Grant Host institution EUROPEAN MOLECULAR BIOLOGY LABORATORY EU contribution € 528 766,34 Address Meyerhofstrasse 1 69117 Heidelberg Germany See on map Region Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis Activity type Research Organisations Principal investigator Takashi Hiiragi (Dr.) Administrative Contact Sonja Noss (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Beneficiaries (2) Sort alphabetically Sort by EU Contribution Expand all Collapse all EUROPEAN MOLECULAR BIOLOGY LABORATORY Germany EU contribution € 528 766,34 Address Meyerhofstrasse 1 69117 Heidelberg See on map Region Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis Activity type Research Organisations Principal investigator Takashi Hiiragi (Dr.) Administrative Contact Sonja Noss (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV Participation ended Germany EU contribution € 621 233,66 Address HOFGARTENSTRASSE 8 80539 Munchen See on map Region Bayern Oberbayern München, Kreisfreie Stadt Activity type Research Organisations Administrative Contact Wilken Yvonne (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
