Wnt signalling in central synaptogenesis. (360G-Wellcome-078764_Z_05_Z)

The formation of synapses requires a proper dialogue between the presynaptic axon and its postsynaptic target cell. Although great progress has been made in understanding the mechanisms that regulate the formation of peripheral synapses much less is known about central synapses. My laboratory has been studying the role of Wnt signalling in the formation of neuronal connections in the vertebrate nervous system. We have demonstrated that Wnts function as retrograde signals that regulate presynapt ic differentiation. Our new studies in the cerebellum have demonstrated that deficiency in Wnt7a and Dvl1, a cytoplasmic protein required for Wnt signalling, results in significant defects in the structure and function of cerebellar synapses. Electrophysiological recordings at the mossy fibre-granule cell synapse reveal a defect in the rate of neurotransmitter release. In the present grant proposal we are taking a multidisciplinary approach that combines transgenic technology, cellular and imag ining techniques and electrophysiology to address the role of Wnt signalling in the assembly and function of central synapses. As Wnt factors are expressed in different areas of the central nervous system, we believe that our studies in the cerebellum will shed light on important general principles used during the assembly of central synapses.