Dendritic development is controlled by Wnt7b-Frizzled7 pathway involving the activation of CaMKII.

FERRARI, MARÍA EDITH; ROSSO SB

Huerta Grande

Congreso; XXVIII Congreso anual de la Sociedad Argentina de Investigaciones en Neurociencia & Reunión satélite/neurobiologia del comportamiento ?Neuroetologia y Neurobiologia de la Memoria en el Cono Sur.; 2013

SAN

Wnts are glycolipoproteins that interact with receptors such as Frizzled, RYK and ROR2 to elicit intracellular responses. This interaction activates 3 cascades: Wnt/β-catenin, planar cell polarity and calcium pathways. In the nervous system, Wnts regulate axon pathfinding, dendrite morphogenesis and synapses formation. In this study, we try to identify the Wnt7b receptor and the role of CaMKII in dendritic development. We found that Wnt7b interacts with Frizzled-7 (Fz7) and increases dendrite complexity. Moreover, Fz7 requires the expression of Dishevelled (DVL), the first downstream effector of Wnt signaling, since a shDVL blocks the effect of Fz7 on dendrite development. In addition, the effect of Fz7 is blocked in neurons expressing the CRD-Fz7 or a shRNA-Fz7. These evidences suggest that Fz7 may act as a receptor of Wnt7b to regulate dendrite morphogenesis. To go further, we examine Wnt-Fz signaling involved in dendritogenesis. We observe that neurons exposed to Wnt show an increase in the level of pCaMKII, a Wnt effector. This effect is blocked when neurons are treated with shRNA against Fz7. Furthermore, treatment with KN-93, a specific CaMKII inhibitor, abolishes the effects of Wnt7b on dendrite growth. Blocking DVL expression by a shDVL inhibits the Fz effect on CaMKII activity. Taken together, our results suggest that Wnt7b-Fz7-Dvl signaling is critical to regulate dendritic development through the activation of CaMKII.