Jonas Muhr's Group
We are trying to understand how neural stem cells are regulated to form the brain. We're also examining the molecular similarities and differences between healthy neural stem cells and cells contributing to the development of brain tumors.
The central nervous system in human is estimated to contain more than 1011 neurons belonging thousands of different sub-types. To understand how this immense array of neural cell types can be generated an important goal of our research is to examine how the developmental competence of neural stem cells is regulated in time and space. In addition, we are examining molecular similarities and differences between somatic stem cells and cells contributing to the development of brain tumors.
We have demonstrated that transcription factors of the Sox family have significant regulatory roles from early to late stages of neural development (Bylund et al., 2003; Sandberg et al., 2005; Bergsland et al., 2006; 2011). An important aim of our research is to understand how different classes of Sox proteins, acting at different stages of neural lineage development, collaborate to regulate the temporal and spatial expression of large sets of neural genes (Fig. 1). To address these questions the laboratory uses a wide range of technologies including gain- and loss-of-function studies in mouse and chick as well as many current methods in molecular biology, including ChIP-seq, mRNA-seq and profiling of DNA and histone modifications.
Another focus of our research is to understand how neural stem cells of the adult brain are prevented from contributing to glioma development. To address this issue we are using mouse genetics to examine the tumor suppressor function of a class of Sox proteins expressed in adult neural stem cells (Fig. 2). With these techniques we can functionally test the potential of neural stem cell expressed Sox proteins in preventing brain tumor development and growth.
|W. Daniel Hagey||Graduate Student|
|Susanne Klum||PhD student|
|Idha Kurtsdotter||Graduate Student|
|Florie Reynaud||Associated, Postdoc|
Sequentially acting Sox transcription factors in neural lineage development.
Genes Dev. 2011 Dec;25(23):2453-64
Activation of neural and pluripotent stem cell signatures correlates with increased malignancy in human glioma.
PLoS ONE 2011 Mar;6(3):e18454
Domain-specific control of neurogenesis achieved through patterned regulation of Notch ligand expression.
Development 2010 Feb;137(3):437-45
SoxB1 transcription factors and Notch signaling use distinct mechanisms to regulate proneural gene function and neural progenitor differentiation.
Development 2008 May;135(10):1843-51
The establishment of neuronal properties is controlled by Sox4 and Sox11.
Genes Dev. 2006 Dec;20(24):3475-86