Molecular dissection of c-Myc function in self renewal/differentiation of neural stem cells
Lead Research Organisation:
Queen Mary University of London
Department Name: Blizard Institute of Cell and Molecular
Abstract
Recent discoveries in cell biology have shown that genes previously implicated in a variety of forms of cancer are also key regulators of the proliferation of normal stem cells. Various signals instruct cells whether to grow or to stop and become a particular cell type. These signals are crucial for proper organ function because the formation of a specific organ depends on the right amount of cell growth being balanced with the right ratio of cells forming differentiated and specialised cells.
Here we will focus on brain stem cells and we will perform experiments to examine the function of particular genes, c-Myc and Bmi1, in regulating basic stem cell properties, such as proliferation/self renewal and differentiation. We hope these studies will provide insight into how neural stem cells are regulated during brain development and in neurogenic area of the adult brain.
Understanding how specific genes promote the proliferation of neural stem cells will allow us to set the basis for a potential future development of new treatments for currently incurable brain diseases and injuries.
Here we will focus on brain stem cells and we will perform experiments to examine the function of particular genes, c-Myc and Bmi1, in regulating basic stem cell properties, such as proliferation/self renewal and differentiation. We hope these studies will provide insight into how neural stem cells are regulated during brain development and in neurogenic area of the adult brain.
Understanding how specific genes promote the proliferation of neural stem cells will allow us to set the basis for a potential future development of new treatments for currently incurable brain diseases and injuries.
Technical Summary
In this proposal, we want to test the hypothesis that the molecular mechanisms that were originally identified to govern c-Myc function in tumourigenesis, also regulate its physiological function in stem cells.
We will use a combined in vitro and in vivo neural stem cell model to address this question. We will take advantage of a unique set of genetically modified mice, which are either already available in our laboratories or which will be generated in the context of this grant application. In particular we plan to generate compound mutant mice overexpressing c-Myc and the Polycomb group gene Bmi1, to assess whether these two genes act synergistically in controlling self renewal and differentiation of subventricular zone neural stem cell. Moreover a combination of genome-wide gene expression analysis and a systematic approach to identify the set of promoters bound by c-Myc and Bmi-1 will be performed on normal and transgenic SVZ stem cells to identify unknown effectors of neural stem cell biological functions.
Understanding the molecular mechanisms regulating the biological properties of neural stem cells is crucial for a potential future development of new therapeutic strategies for brain diseases and injuries, which are currently characterised by a dismal prognosis.
We will use a combined in vitro and in vivo neural stem cell model to address this question. We will take advantage of a unique set of genetically modified mice, which are either already available in our laboratories or which will be generated in the context of this grant application. In particular we plan to generate compound mutant mice overexpressing c-Myc and the Polycomb group gene Bmi1, to assess whether these two genes act synergistically in controlling self renewal and differentiation of subventricular zone neural stem cell. Moreover a combination of genome-wide gene expression analysis and a systematic approach to identify the set of promoters bound by c-Myc and Bmi-1 will be performed on normal and transgenic SVZ stem cells to identify unknown effectors of neural stem cell biological functions.
Understanding the molecular mechanisms regulating the biological properties of neural stem cells is crucial for a potential future development of new therapeutic strategies for brain diseases and injuries, which are currently characterised by a dismal prognosis.
