WNT signalling through Dishevelled, Rac and JNK regulates dendritic development.

ROSSO S.; SUSSMAN D; WYNSHAW-BORIS A; SALINAS P

NATURE NEUROSCIENCE.

Nature Publishing Group

Lugar: New York; Año: 2005 vol. 8 p. 34 - 42

1097-6256

Dendritic arborization is required for proper neuronal connectivity. Rho GTPases have been implicated in the regulation of dendrite development. However, the signalling 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 expression of Dishevelled (Dvl) and is blocked by Sfrp1, a secreted Wnt antagonist. Consistent with these findings, hippocampal neurons from Dvl1 mutant mice exhibit reduced dendritic arborization. Activation of the canonical Wnt-Gsk3ß pathway does not affect dendritic development. In contrast, Wnt7b and Dvl activate Rac and JNK in hippocampal neurons. Importantly, dominant-negative Rac, dominant negative JNK or inhibition of JNK blocks Dvl-mediated dendritic growth. These findings demonstrate a novel function for the non-canonical Wnt pathway in dendrite development and identify Dvl as a regulator of Rho GTPases and JNK during dendritic morphogenesis.