NEUROGENESIS · Control of neurogenesis in vertebrate brain
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2008-04-01 → 2010-03-31
- EU contribution
- €167,664
- Participants
- 1
- Scheme
- EIF
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Results in brief
Final Activity and Management Report Summary - NEUROGENESIS (Control of neurogenesis in vertebrate brain)
We investigated the mechanisms that control the generation of neurons in the vertebrate brain - this process is called neurogenesis. Our aim was to understand how stem cell behaviour is regulated. Stem cell behaviour involves the ability of cells to divide to generate more cells (called daughter cells) some of which are more stem cells and others of which are the neurons of the brain themselves. These types of cell divisions are called asymmetric divisions. We tested the hypothesis that asymmetric divisions are regulated by specialised proteins present in the stem cells becoming segregated to different daughter cells - this hypothesis is called asymmetric inheritance. We were able to visualize asymmetric inheritance of proteins for the first time in an intact vertebrate embryo brain and we show that asymmetric inheritance is at least partially responsible for stem cell behaviour. Our work also found a completely unexpected aspect of asymmetric division that contradicts previous hypotheses. We show that the cells that become neurons in asymmetric divisions originate from the daughters that had previously been thought to generate more stem cells. This is an important new observation that potentially changes the way scientists think about stem cell behaviour in vertebrate embryo brains.
Data: CORDIS, © European Union
Project objective
Cell diversity may arise at the moment of cell division when the cytoplasmatic determinants or membrane properties are asymmetrically distributed to the daughter cells. The asymmetric cell divisions rely therefore on the co-ordination of cell fate determinant localisation with the mitotic cleavage plan.This proposal will test the novel hypothesis that components of the vertebrate Planar Cell Polarity (PCP) pathway play critical roles in the control of progenitor divisions and neuronal fate determination in the vertebrate brain. We have evidence that the transmembrane protein Vangl2 is asymmetrically localised within zebrafish neuronal progenitors and may be required to determine orientation of progenitor cell mitoses.We will use zebrafish embryos to explore the regulation of Vangl2 localisation and the possibility that Vangl2 and other members of the PCP pathway are important regulators of neurogenesis. We will also determine whether the defective neurogenesis could be linked to the mitotic cleavage plan.And finally, whether PCP pathway controls the localisation of the cell fate determinant, Numb. Understanding the development and function of the brain is a key goal for research within the European Research Area.This work will greatly increase our knowledge of the molecular mechanisms controlling the neurogenesis, a fundamental step in brain development. We will use the zebrafish embryo as this allows single cell visualization and a quick and successful analysis of gene function.Together with the previous experience in classical embryology, this training will provide the candidate with new scientific and technical skills important to becoming an independent scientist.
Original text from CORDIS.
Participants
- KING'S COLLEGE LONDON · LONDONCoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union