WNT7B and FRIZZLED7 are involved in the regulation of dendrite architecture by the non-canonical WNT pathways

FERRARI, MARÍA EDITH; ROSSO, SB

Huerta Grande

Congreso; XIX Congreso Anual de la Sociedad Argentina de Investigaciones en Neurociencia; 2014

Sociedad Argentina de Investigación en Neurociencia.

Wnt proteins are well known morphogens that interact with membrane receptors such as Frizzled (Fz), Ryk, Ror and IGF-1R, activating at least three signalling pathways: Wnt/β-catenin, planar cell polarity (PCP) and Calcium pathways. In the nervous system, Wnt proteins regulate neuronal polarization and migration, axon pathfinding, dendrite morphogenesis and synapse formation. Previously, we identified the transmembrane Frizzled7 (Fz7) protein as a potential Wnt7b receptor to regulate dendrite formation. Currently, we examined the contribution of the non-canonical Calcium pathway on dendritic development. Our observations indicated that Wnt7b-Fz7 regulate dendrite development through the activation of CaMKII. Furthermore, we evaluated the participation of the PCP pathway and its effector JNK on the dendrite growth induced by Wnt7b-Fz7. We found that hippocampal neurons exposed to Wnt7b, as well as those overexpressing Fz7, exhibited an increase in the activity of CaMKII and JNK. In addition, the inhibition of CaMKII using a specific shRNA, blocked the Wnt7b and Fz7 effects on dendrite morphogenesis. These evidences show that Wnt7b and Fz7 would play a key role in dendrite development and complexity, through the PCP and Calcium pathways, suggesting a potential overlapping of the two non-canonical Wnt signaling in this process.