WNT-7a induces axonal remodeling and increases synapsin I levels in cerebellar neurons

WNT factors play a key role in early patterning of the embryo. However, expression of Wnt genes after cell commitment suggests additional roles in later developmental processes. We report here that Wnt-7a is expressed in cerebellar granule cell neurons as they begin to extend processes and form synapses. WNT-7a increases axonal spreading and branching in cultured granule cells. Moreover, WNT-7a increases the levels of synapsin I, a presynaptic protein involved in synapse formation and function. Lithium mimics WNT-7a in granule cells by inhibiting GSK-3beta, a component of the WNT signaling pathway. These results suggest a direct effect of WNT-7a in the regulation of neuronal cytoskeleton and synapsin I in granule cell neurons. We propose that WNT proteins have a novel function in the formation of neuronal connections.