Wnt-Dvl signalling regulates dendrite morphogenesis.

ROSSO SB

Puerto Varas

Congreso; Chilean Society for Cell Biology XXVII Annual Meeting; 2013

Chilean Society for Cell Biology

Wnt signalling pathway plays a key role in the central nervous system development. Growing evidence indicate that Wnt proteins regulate the structure and function of the adult nervous system. Wnt components are key regulators of a variety of developmental processes, including embryonic patterning, cell specification, and cell polarity. In the nervous system, Wnt signaling also regulates the formation and function of neuronal circuits by controlling neuronal differentiation, axon outgrowth and guidance, dendrite development, synaptic function and neuronal plasticity. Wnts signal through different receptors including Frizzled family, the LRP5/6 coreceptors, and the tyrosine-kinase receptors as ROR2 and RYK. New evidence suggest that Wnt proteins can also modulate neuronal morphogenesis through the IGF-1 receptor-PI3K pathway activation. We previously demonstrated that Wnt7b regulates dendrite maturation through a non canonical pathway. Particularly, Wnt and DVL signal through Rac and JNK to regulate dendrite development. Currently, we perform assays to identify the Wnt7b receptor involved in the dendritic effect. Binding experiments on cell surface show that Wnt7b interacts with extracellular domain of Frizzled-7 (Fz7). Importantly, Fz7 expressing neurons develop complex dendritic arbours compared to controls. In addition, this effect is blocked by a Fz7 dominant negative or a Fz-7 shRNA. These evidences suggest that Fz7 may function as a transmembrana receptor of Wnt7b to regulate dendrite morphogenesis. To go further, we analyze the intracellular signalling pathway involved in the Wnt7b-Fz7 effect. Our data suggest that Wnt7b also activates CaMKII cascade in cultured hippocampal neurons. This effect is blocked when neurons are treated with Sfrp1, a secreted Wnt antagonist. Furthermore, loss of function experiments using a CaMKII shRNA or a CaMKII inhibitor abolishes the effects of Wnt7b on dendrite growth. Taken together, our findings indicate that Wnt7b-Fz7 signaling is critical to modulate dendrite morphogenesis through the activation of CaMKII. This project is supported by CONICET, FONCyT and UNR, Argentina.