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.
Lucas
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FR
Developmental Biology Research Centre, The Randall Institute, King's College London, 26-29 Drury Lane, London, WC2B 5RL, United Kingdom.
Salinas
P C
PC
D000818:Animals; D001369:Axons / Q000648:ultrastructure*; D001714:Bipolar Disorder / Q000188:drug therapy / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D017403:In Situ Hybridization; D008094:Lithium / Q000494:pharmacology; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012313:RNA / Q000235:genetics / Q000378:metabolism; D016704:Synapsins / Q000378:metabolism*; D051153:Wnt Proteins
D011518:Proto-Oncogene Proteins; D016704:Synapsins; C092778:WNT7A protein, human; D051153:Wnt Proteins; C490508:Wnt7a protein, mouse; D012313:RNA; D008094:Lithium