How does Sox9 confer neural stem cell status?
Dr Robin Lovell-Badge, National Institute for Medical Research/Division of Biosciences
Description of Project:
A neural stem cell (NSC)is defined by its ability to generate new NSCs (self-renewal) and to differentiate to give rise to each of the three main lineages of the central nervous system, namely neurons, astrocytes and oligodendrocytes. Consequently, much interest has focused on understanding the molecular mechanisms that specify the properties of NSCs. It has become clear that NSCs are not simply cells whose developmental potential has become restricted to neural lineages during development; instead these cells appear to be ‘induced’ from a population of neuroepithelial cells (NECs). Data from our lab suggests that this transition coincides with the expression of SOX9, a member of the class E group of HMG box-containing SOX transcription factors. SOX9 appears sufficient to induce cells with NSC-like properties. Moreover, preliminary evidence indicates that this transcription factor is required for NSC formation. I intend to test this hypothesis by verifying the requirement for Sox9. In addition, I hope to identify the downstream targets of SOX9 in order to understand how it confers stem cell properties on neuroepithelial precursors.