The Planar Cell Polarity Transmembrane Protein Vangl2 Promotes Dendrite, Spine and Glutamatergic Synapse Formation in the Mammalian Forebrain.
The transmembrane protein Vangl2, a key regulator of the Wnt/planar cell polarity (PCP) pathway, is involved in dendrite arbor elaboration, dendritic spine formation and glutamatergic synapse formation in mammalian central nervous system neurons. Cultured forebrain neurons from Vangl2 knockout mice have simpler dendrite arbors, fewer total spines, less mature spines and fewer glutamatergic synapse inputs on their dendrites than control neurons. Neurons from mice heterozygous for a semidominant Vangl2 mutation have similar but not identical phenotypes, and these phenotypes are also observed in Golgi-stained brain tissue from adult mutant mice. Given increasing evidence linking psychiatric pathophysiology to these subneuronal sites and structures, our findings underscore the relevance of core PCP proteins including Vangl2 to the underlying biology of major mental illnesses and their treatment.
Department of Neurology and Neurological Sciences, Stanford University, Palo Alto, Calif., USA; Department of Psychiatry, Stanford University, Palo Alto, Calif., USA.
Nathan D
ND
Okerlund
Department of Psychiatry, Stanford University, Palo Alto, Calif., USA; Tetrad Graduate Program, Stanford University, Palo Alto, Calif., USA.
Robert E
RE
Stanley
Department of Psychiatry, Stanford University, Palo Alto, Calif., USA; Tetrad Graduate Program, Stanford University, Palo Alto, Calif., USA; UCSF Weill Institute for Neurosciences, University of California, San Francisco (UCSF), San Francisco, Calif., USA; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco (UCSF), San Francisco, Calif., USA.
Benjamin N R
BN
Cheyette
Dendrite; Forebrain; Planar cell polarity; Pyramidal neuron; Spine; Synapse; Vangl2; Wnt