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MAMMALIANDEVELOPMENT

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A systems level understanding of the novel principle in early mammalian developm...

A systems level understanding of the novel principle in early mammalian development 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 esta... ver más

31/12/2013

EMBL

1M€

Presupuesto del proyecto: 1M€

Líder del proyecto

EUROPEAN MOLECULAR BIOLOGY LABORATORY No se ha especificado una descripción o un objeto social para esta compañía.

Fecha límite participación Sin fecha límite de participación.

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Financiación concedida El organismo FP7 notifico la concesión del proyecto el día 2013-12-31 No tenemos la información de la convocatoria

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2 Participantes

EMBL

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MPG

N.D. | Participante

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Líder del proyecto

EUROPEAN MOLECULAR BIOLOGY LABORATORY No se ha especificado una descripción o un objeto social para esta compañía.

Presupuesto del proyecto 1M€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto 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.

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