Molecular Mechanism for Primordial Germ Cell Specification - The Role of Blimp1

Objective

Germ cells serve the critical function of transmitting genetic and epigenetic information across generations in multi-cellular organisms. An important attribute of the germ line is to generate the totipotent state. Studies of this unique cell lineage are of wide general interest in the context of stem cells and mechanisms of pluripotency. Relatively little is yet known about how germ cells are specified in mice. Recent genetic studies showed that the transcriptional repressor Blimp1 is a critical determinant of germ cell fate in the epiblast cells of the mouse embryo. There are only about 35 founder primordial germ cells (PGCs) present in each embryo, providing a significant hurdle for the mechanistic elucidation of germ cell specification. A robust in-vitro system that mimics PGC specification is essential to gain a deeper insight into the role of Blimp1 in germ cell fate determination. This project aims to generate such a system using a twofold approach. First, by engineering embryonic stem cells to express Blimp1 in an inducible manner and utilizing them for the induction of PGC fate. Second, by generating transgenic mice expressing fluorescent reporter molecules, for the derivation of epiblast stem cell cultures and subsequent FACS sorting of PGCs. To elucidate the gene expression programme governed by Blimp1 during PGC specification, the culture models will be used for analysis of the genome wide target site binding of Blimp1 and performing functional assays of the target genes and co-repressor proteins bound with Blimp1 to the sites identified. This will likely provide novel biochemical insight into PGC specification revealing mechanisms underlying the balance between pluripotency and differentiation. The project will provide training to the fellow in terms of techniques and subjects pertaining to stem cells, germ cells, mouse genetics and development, while at the same time allowing the re-integration of the fellow into the European scientific community.

Fields of science (EuroSciVoc)

CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.

• natural sciences biological sciences biochemistry
• medical and health sciences medical biotechnology genetic engineering
• medical and health sciences medical biotechnology cells technologies stem cells

Keywords

Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)

• Mouse developmental biology
• Natural sciences
• chromatin
• embryonic stem cells
• epigenetics
• lineage specification
• primordial germ cells
• stem cells
• transcription factors

Programme(s)

Multi-annual funding programmes that define the EU’s priorities for research and innovation.

• FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)

Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

• FP7-PEOPLE-IEF-2008 - Marie Curie Action: "Intra-European Fellowships for Career Development"

Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

FP7-PEOPLE-IEF-2008
See other projects for this call

Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

MC-IEF - Intra-European Fellowships (IEF)

Coordinator