The role of growth factors in the formation and maintenance of central synapses. (360G-Wellcome-075064_Z_04_A)

We have shown that Wnt deficiency affects presynaptic differentiation in the mouse cerebellum. Conversely gain of function studies showed that Wnts increase presynaptic differentiation in cerebellar and hippocampal neurons. More recently we found that Wnt signalling also regulates neurotransmitter release. The presence of other growth factors such as FGFs and Shh during the synaptogenic period suggests that Wnts don't act alone. Indeed, a recent study showed that FGF22 regulates synaptic differentiation at the mossy fibre-granule cell synapse, the same synapse where Wnt7a acts as a synaptogenic factor. These findings suggest that FGF and perhaps Shh might collaborate with Wnts during central synaptogenesis. In this project, the student will examine 1) The role of FGFs and Shh in central synaptogenesis using our in vitro hippocampal and cerebellar systems. 2) The function of FGFs and Shh in Wnt-mediated synaptic activity. 3) The consequence of loss of function of Wnt, FGF and Shh signalling in synapse formation in the vertebrate nervous system.