Axonal remodeling and synaptic differentiation in the cerebellum is regulated by WNT-7a signaling.
Synapse formation requires changes in cell morphology and the upregulation and localization of synaptic proteins. In the cerebellum, mossy fibers undergo extensive remodeling as they contact several granule cells and form complex, multisynaptic glomerular rosettes. Here we show that granule cells secrete factors that induce axon and growth cone remodeling in mossy fibers. This effect is blocked by the WNT antagonist, sFRP-1, and mimicked by WNT-7a, which is expressed by granule cells. WNT-7a also induces synapsin I clustering at remodeled areas of mossy fibers, a preliminary step in synaptogenesis. Wnt-7a mutant mice show a delay in the morphological maturation of glomerular rosettes and in the accumulation of synapsin I. We propose that WNT-7a can function as a synaptogenic factor.
Hall
A C
AC
Developmental Biology Research Centre, The Randall Institute, King's College London, United Kingdom.
Lucas
F R
FR
Salinas
P C
PC
D000818:Animals; D001369:Axons / Q000502:physiology* / Q000648:ultrastructure; D001685:Biological Factors / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D002454:Cell Differentiation; D002478:Cells, Cultured; D002525:Cerebellar Cortex / Q000166:cytology* / Q000196:embryology; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D003712:Dendrites / Q000502:physiology / Q000648:ultrastructure; D038362:Glycogen Synthase Kinase 3; D006023:Glycoproteins; D020439:Growth Cones / Q000502:physiology*; D007294:Inositol / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D008094:Lithium / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009412:Nerve Fibers / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D015398:Signal Transduction; D013569:Synapses / Q000502:physiology; D016704:Synapsins / Q000378:metabolism; D014162:Transfection; D051153:Wnt Proteins; D000099274:Frizzled-Related Proteins
D001685:Biological Factors; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D017077:Culture Media, Conditioned; D016895:Culture Media, Serum-Free; D038362:Glycogen Synthase Kinase 3; D006023:Glycoproteins; D007294:Inositol; D047908:Intracellular Signaling Peptides and Proteins; D008094:Lithium; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D016704:Synapsins; D051153:Wnt Proteins; D000099274:Frizzled-Related Proteins; C490508:Wnt7a protein, mouse