Genetic dissection of intercellular signalling during development of the mammalian cerebellum. (360G-Wellcome-091475_Z_10_Z)

The cerebellum is an attractive system for investigating fundamental processes in developmental neurobiology. A key question is how different neuronal and glial cell types communicate with each other to coordinate processes such as cell proliferation. To determine whether cells in the developing cerebellum utilise the Fibroblast Growth Factor (FGF) signalling pathway to communicate, we produced mice in which FGF antagonists, encoded by the Sprouty genes, had been deleted from the onset of cerebe llar development. We uncovered a novel route through which the proliferation of granule cell precursors (GCps) could be regulated. We hypothesise that Bergmann glia, previously only thought to have roles in guiding cell migration, are important sources of the GCp mitogen, Sonic Hedgehog (SHH) and that the differentiation of these glia and their ability to produce SHH, are controlled by the level of FGF signalling. We will use cell type-specific gene deletion experiments to dissect the roles of F GF and SHH signalling in Bergmann glia and other cells like Purkinje neurons in the developing cerebellum. Our studies will provide insights into how different cell types utilise these conserved signalling molecules to communicate with each other to coordinate the formation of a vital part of the central nervous system.