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A systems-level understanding of the novel principle in early mammalian development

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.

Field of science

  • /natural sciences/biological sciences/zoology/mammalogy
  • /medical and health sciences/clinical medicine/embryology

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
Address
Meyerhofstrasse 1
69117 Heidelberg
Germany
Activity type
Research Organisations
EU contribution
€ 528 766,34
Principal investigator
Takashi Hiiragi (Dr.)
Administrative Contact
Sonja Noss (Ms.)

Beneficiaries (2)

EUROPEAN MOLECULAR BIOLOGY LABORATORY
Germany
EU contribution
€ 528 766,34
Address
Meyerhofstrasse 1
69117 Heidelberg
Activity type
Research Organisations
Principal investigator
Takashi Hiiragi (Dr.)
Administrative Contact
Sonja Noss (Ms.)
MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV

Participation ended

Germany
EU contribution
€ 621 233,66
Address
Hofgartenstrasse 8
80539 Munich
Activity type
Other
Administrative Contact
Wilken Yvonne (Ms.)