CORDIS
EU research results

CORDIS

English EN
Cell division and the origin of embryonic aneuploidy in preimplantation mouse development

Cell division and the origin of embryonic aneuploidy in preimplantation mouse development

Objective

Cell division is fundamental for development. In the early mammalian embryo it drives the rapid proliferation of totipotent cells, the basis for forming the fetus. Given its crucial importance, it is surprising that cell division is particularly error-prone at the beginning of mammalian life, resulting in spontaneous abortion or severe developmental retardation, the incidence of which is increasing with age of the mother. Why aneuploidy is so prevalent and how early embryonic development nevertheless achieves robustness is largely unknown. The goal of this project is a comprehensive analysis of cell divisions in the mouse preimplantation embryo to determine the molecular mechanisms underlying aneuploidy and its effects on normal development. Recent technological breakthroughs, including light sheet microscopy and rapid loss-of-function approaches in the mouse embryo will allow us for the first time to tackle the molecular mechanisms of aneuploidy generation and establish the preimplantation mouse embryo as a standard cell biological model system. For that purpose we will develop next generation light sheet microscopy to enable automated chromosome tracking in the whole embryo. Mapping of cell division errors will reveal when, where, and how aneuploidy occurs, what the fate of aneuploid cells is in the embryo, and how this changes with maternal age. We will then perform high resolution functional imaging assays to identify the mitotic pathways responsible for aneuploidy and understand why they do not fully function in early development. Key proteins will be functionally characterised in detail integrating light sheet imaging with single molecule biophysics in embryos from young and aged females to achieve a mechanistic understanding of the unique aspects of cell division underlying embryonic aneuploidy. The achieved knowledge gain will have an important impact for our understanding of mammalian, including human infertility.
Leaflet | Map data © OpenStreetMap contributors, Credit: EC-GISCO, © EuroGeographics for the administrative boundaries

Host institution

EUROPEAN MOLECULAR BIOLOGY LABORATORY

Address

Meyerhofstrasse 1
69117 Heidelberg

Germany

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 2 497 156

Beneficiaries (1)

Sort alphabetically

Sort by EU Contribution

Expand all

EUROPEAN MOLECULAR BIOLOGY LABORATORY

Germany

EU Contribution

€ 2 497 156

Project information

Grant agreement ID: 694236

Status

Ongoing project

  • Start date

    1 January 2017

  • End date

    31 December 2021

Funded under:

H2020-EU.1.1.

  • Overall budget:

    € 2 497 156

  • EU contribution

    € 2 497 156

Hosted by:

EUROPEAN MOLECULAR BIOLOGY LABORATORY

Germany