Wnt-7a Stimulates Dendritic Spine Morphogenesis and PSD-95 Expression Through Canonical Signaling

• Published in: Molecular neurobiology Vol. 56; no. 3; pp. 1870 - 1882
• Main Authors: Ramos-Fernández, Eva, Tapia-Rojas, Cheril, Ramírez, Valerie T., Inestrosa, Nibaldo C.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-03-2019; Springer Nature B.V
• Subjects: Biomedical and Life Sciences; Biomedicine; Cell Biology; Dendritic spines; Glycogen; Glycogen synthase kinase 3; Hippocampal plasticity; Hippocampus; Kinases; LEF protein; Lymphocytes T; Morphogenesis; Neurobiology; Neurology; Neurosciences; Postsynaptic density; Postsynaptic density proteins; Spatial memory; Spine; Synaptic plasticity; Synaptogenesis; Transcription; Wnt protein; β-Catenin; Wnt signaling; Dendritic spine plasticity; TCF/LEF; PSD-95
• ISSN: 0893-7648; 1559-1182
• DOI: 10.1007/s12035-018-1162-1

Wnt signaling regulates brain development and synapse maturation; however, the precise molecular mechanism remains elusive. Here, we report that Wnt-7a stimulates dendritic spine morphogenesis in the hippocampus via glycogen synthase kinase-3 β (GSK-3β) inhibition, triggering β-catenin/T cell factor/lymphoid enhancer factor (TCF/LEF)-dependent gene transcription and promoting postsynaptic density-95 (PSD-95) protein expression. In addition, wild-type mice treated with an inhibitor of β-catenin/TCF/LEF-mediated transcription showed a reduction in spatial memory acquisition accompanied by a reduction in PSD-95 and decreases in spine density measured by Golgi staining, suggesting that PSD-95 is a novel Wnt target gene. Together, our data strongly demonstrate that Wnt-dependent target gene transcription is essential to hippocampal synaptic plasticity.