Frizzled-7, a potential Wnt7b receptor, regulates dendrite morphogenesis.

PHILIPPE, VALERIA ; ROSSO SILVANA

Huerta Grande

Congreso; II REUNIÓN CONJUNTA DE NEUROSCIENCIA; 2010

Sociedad Argentina de Neurociencia

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. The morphogenesis of dendrites is regulated by genetic factors, neuronal activity, and external molecular cues. WNTs are secreted glycoproteins that signal through their Frizzled receptors (FZ) and Dishevelled (DVL). They can signal through three different pathways: WNT/β-catenin pathway, the planar cell polarity and the calcium pathway. We demonstrated that Wnt7b regulates dendritic morphogenesis. 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 Fz7 (CRD-Fz7). In addition, Fz7 expressing neurons develop complex dendritic arbours compared to controls. Neurons show a significant increase in dendritic length and complexity. Importantly, this effect is blocked when neurons express the CRD domain of Fz7, which function as a dominant negative. These evidences suggest that Fz7 may act as a potential transmembrana receptor of Wnt7b to regulate dendrite morphogenesis