Editing Synaptogenesis (section)

===Central nervous system===

Wnt family members contribute to synapse formation in the [[cerebellum]] by inducing [[presynaptic]] and [[postsynaptic]] terminal formation. This brain region contains three main neuronal cell types- [[Purkinje cells]], [[Granule cell (cerebellum)|granule]] cells and [[Mossy fiber (cerebellum)|mossy fiber]] cells. Wnt-3 expression contributes to Purkinje cell [[neurite]] outgrowth and synapse formation.<ref name="budnik">{{cite journal | vauthors = Budnik V, Salinas PC | title = Wnt signaling during synaptic development and plasticity | journal = Current Opinion in Neurobiology | volume = 21 | issue = 1 | pages = 151–159 | date = February 2011 | pmid = 21239163 | pmc = 3499977 | doi = 10.1016/j.conb.2010.12.002 }}</ref><ref name="speese">{{cite journal | vauthors = Speese SD, Budnik V | title = Wnts: up-and-coming at the synapse | journal = Trends in Neurosciences | volume = 30 | issue = 6 | pages = 268–275 | date = June 2007 | pmid = 17467065 | pmc = 3499976 | doi = 10.1016/j.tins.2007.04.003 | series = 6 }}</ref> Granule cells express Wnt-7a to promote axon spreading and branching in their synaptic partner, mossy fiber cells.<ref name="speese" /> [[wikt:retrograde|Retrograde]] secretion of Wnt-7a to mossy fiber cells causes [[growth cone]] enlargement by spreading [[microtubules]].<ref name="speese" /> Furthermore, Wnt-7a retrograde signaling recruits [[synaptic vesicles]] and presynaptic proteins to the synaptic [[active zone]].<ref name="budnik" /> Wnt-5a performs a similar function on postsynaptic granule cells; this Wnt stimulates receptor assembly and clustering of the scaffolding protein [[PSD-95]].<ref name="budnik" />

In the [[hippocampus]] Wnts in conjunction with cell electrical activity promote synapse formation. Wnt7b is expressed in maturing dendrites,<ref name="speese" /> and the expression of the Wnt receptor [[Frizzled]] (Fz), increases highly with synapse formation in the hippocampus.<ref name="budnik" /> [[NMDA receptor|NMDA]] [[glutamate]] receptor activation increases Wnt2 expression. [[Long term potentiation]] (LTP) due to NMDA activation and subsequent Wnt expression leads to Fz-5 localization at the postsynaptic active zone.<ref name="budnik" /> Furthermore, Wnt7a and Wnt2 signaling after NMDA receptor mediated LTP leads to increased [[dendritic arborization]] and regulates activity induced synaptic plasticity.<ref name="park">{{cite journal | vauthors = Park M, Shen K | title = WNTs in synapse formation and neuronal circuitry | journal = The EMBO Journal | volume = 31 | issue = 12 | pages = 2697–2704 | date = June 2012 | pmid = 22617419 | pmc = 3380216 | doi = 10.1038/emboj.2012.145 }}</ref> Blocking Wnt expression in the hippocampus mitigates these activity dependent effects by reducing dendritic arborization and subsequently, synaptic complexity.<ref name="park" />