Dendrite development is modulated by Wnt7b-Fz7 through activation of non canonical wnt pathways.

LUNA, S.; FERRARI, ME;; CASADEI, IM ; AND ROSSO SB.

Buenos Aires

Congreso; 2nd FALAN Congress, Federation of Latin American and Caribbean Neuroscience Societies.; 2016

Brain wiring begins during embryonic development and relies on crucial processes regulated by molecular mechanisms. Neuronal polarization and dendrite morphogenesis are key events that lead to the proper functioning of the nervous system and are orchestrated by morphogens. Among this, Wnt proteins stand out as essential molecules that bind to their membrane receptors, such as Frizzled (Fz), activating three pathways: Wnt/b-catenin (canonical), planar cell polarity (PCP) and Calcium (non canonical). We focused our research on the interaction of Wnt7b and its receptor, and their effects on dendrite architecture. Using hippocampal cultured neurons we identified Fz7 as a specific Wnt7b receptor and analyzed its temporal expression through in vitro and in vivo assays.Then, we studied how Wnt7b through Fz7 modulates neuronal development and observed that neurons overexpressing Fz7 or exposed to Wnt7b exhibited more branches and longer dendrites, thus, a more complex dendritic arbours.Furthermore, we evaluated the involvement of non canonical Wnt pathways in these morphological changes, through the PCP and Calcium effectors, JNK and CaMKII, respectively. The inhibition of these proteins blocked Wnt7b-Fz7 effects, since neurons exhibited less complex dendritic architecture. On the contrary, we found an increase in JNK and CaMKII activity in those neurons. In conclusion, Fz7 acts as Wnt7b receptor and both of them are involved in dendritogenesis through the non canonical Wnt pathways.