Implications of Wnt/Fz signaling pathways on axonal development

LORENA PAOLA NEILA; MARIA EDITH FERRARI ; SILVANA B. ROSSO

Mar del Plata

Congreso; XXXII CONGRESO ANUAL SAN 2017; 2017

Sociedad Argentina de Investigación en Neurociencias

Neuronal morphogenesis is crucial on brain development and requires complex signaling carried out by several molecules, such as Wnts. These ligands bind to receptors of the Frizzled (Fz) family, activating 3 pathways: Wnt/-catenin, planar cell polarity (PCP) and Calcium. Our research focused on Wnt7b and its participation on neuronal development. Initially, we identified Fz7 as Wnt7b receptor and characterized its temporal and spatial expression in neurons. We found that Fz7 expression increased over time and is located on the cell body, dendrites and spines. According to this, we then evaluate the role of Wnt7b-Fz7 on dendritogenesis and observed that neurons exposed to Wnt7b or those overexpressing Fz7 developed more complex dendritic arbours. That effect was blocked when Fz7 is suppressed. To go further, we examined the intracellular signaling triggered by Wnt7b-Fz7 interaction and found that both CaMKII (Wnt/Ca2+pathway) and JNK (PCP pathway) are involved on its effects over dendritic architecture. Based on these previous results, we decided to evaluate the contribution of Wnt7b-Fz7 during earlier periods, particularly on axonal growth. We analyzed pyramidal neurons at early stages of development and observed that Fz7 is present along neurites and mainly at the growth cones. Furthermore, through Fz7 overexpression in neurons we noted it had an effect on axonal outgrowth. More analyses are yet to be performed in order to fully evaluate Wnt7b-Fz7 role on axon development.