Wnt signaling through Dishevelled, Rac and JNK regulates dendritic development.
Dendritic arborization is required for proper neuronal connectivity. Rho GTPases have been implicated in the regulation of dendrite development. However, the signaling pathways that impinge on these molecular switches remain poorly understood. Here we show that Wnt7b, which is expressed in the mouse hippocampus, increases dendritic branching in cultured hippocampal neurons. This effect is mimicked by the expression of Dishevelled (Dvl) and is blocked by Sfrp1, a secreted Wnt antagonist. Consistent with these findings, hippocampal neurons from mice lacking Dvl1 show reduced dendritic arborization. Activation of the canonical Wnt-Gsk3beta pathway does not affect dendritic development. In contrast, Wnt7b and Dvl activate Rac and JNK in hippocampal neurons. Dominant-negative Rac, dominant-negative JNK or inhibition of JNK blocks Dvl-mediated dendritic growth. These findings demonstrate a new function for the non-canonical Wnt pathway in dendrite development and identify Dvl as a regulator of Rho GTPases and JNK during dendritic morphogenesis.
Rosso
Silvana B
SB
Department of Anatomy and Developmental Biology, Rockefeller Building, University College London, University Street, London WC1E 6BT, UK.
Sussman
Daniel
D
Wynshaw-Boris
Anthony
A
Salinas
Patricia C
PC
D000209:Acute-Phase Proteins / Q000502:physiology; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D003712:Dendrites / Q000502:physiology* / Q000648:ultrastructure; D000072261:Dishevelled Proteins; D004622:Embryo, Mammalian; D006023:Glycoproteins / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D015398:Signal Transduction; D014018:Tissue Distribution; D051153:Wnt Proteins; D020744:rac GTP-Binding Proteins / Q000378:metabolism*
D000209:Acute-Phase Proteins; D048868:Adaptor Proteins, Signal Transducing; D000072261:Dishevelled Proteins; C000606579:Dvl1 protein, mouse; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins; C095937:Wnt7b protein, mouse; C010781:acute-phase protein rho; D048031:JNK Mitogen-Activated Protein Kinases; D020744:rac GTP-Binding Proteins