Wnt7b-DVL signaling regulates dendrite development through the activation of Frizzled-7 receptor.

FERRARI, MARÍA EDITH; BERNIS MARÍA EUGENIA ; ROSSO SILVANA

Buenos Aires

Simposio; II Simposio Franco-Argentino de Neurociencias,; 2012

Wnt factors comprise a family of secreted glycolipoproteins able to interact with cell surface receptors eliciting a variety of intracellular responses. To date, 19 distinct Wnts have been identified in mammals. The diversity of the Wnt expression is highly conserved among animal species. Wnts can signal through different receptors including Frizzled family, the LRP5/6 coreceptors, and the tyrosine-kinase receptors as ROR2 and RYK. Binding of Wnts to their receptors activates a number of intracellular cascades: WNT/β-catenin pathway, the planar cell polarity and the calcium pathway. Wnt factors play a crucial role in the embryonic development of all animal species. In the nervous system, WNTs regulates neuronal connectivity by controlling axon pathfinding, dendrite morphogenesis and synapses. Previously, we demonstrated that Wnt7b regulates dendritic maturation. Thus, Wnt-DVL signals through Rac and JNK to regulate dendrite development. In this study, we go further and we try to identify the Wnt7b receptor involved in the dendritic effect. Binding assays on cell surfaces show that Wnt7b interacts with extracellular domain of Frizzled-7 (Fz7) (CRD-Fz7). Importantly, Fz7 expressing neurons develop complex dendritic arbours compared to controls. These neurons show a significant increase in dendritic length and complexity. In addition, this effect is blocked when neurons express the CRD domain of Fz7, which function as a dominant negative. Additional experiments show that the expression of a shRNA of Fz-7 blocks the Wnt7b dendritic effect. These evidences suggest that Fz7 may act as a transmembrana receptor of Wnt7b to regulate dendrite morphogenesis.