Neurotrophin and Wnt signaling cooperatively regulate dendritic spine formation

Mol Cell Neurosci. 2013 Sep;56:115-27. doi: 10.1016/j.mcn.2013.04.006. Epub 2013 Apr 30.

Abstract

Dendritic spines are major sites of excitatory synaptic transmission and changes in their numbers and morphology have been associated with neurodevelopmental and neurodegenerative disorders. Brain-derived Neurotrophic Factor (BDNF) is a secreted growth factor that influences hippocampal, striatal and neocortical pyramidal neuron dendritic spine density. However, the mechanisms by which BDNF regulates dendritic spines and how BDNF interacts with other regulators of spines remain unclear. We propose that one mechanism by which BDNF promotes dendritic spine formation is through an interaction with Wnt signaling. Here, we show that Wnt signaling inhibition in cultured cortical neurons disrupts dendritic spine development, reduces dendritic arbor size and complexity, and blocks BDNF-induced dendritic spine formation and maturation. Additionally, we show that BDNF regulates expression of Wnt2, and that Wnt2 is sufficient to promote cortical dendrite growth and dendritic spine formation. Together, these data suggest that BDNF and Wnt signaling cooperatively regulate dendritic spine formation.

Keywords: BDNF; Dendrite branching; Dendritic spine; Synapse; Wnt signaling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Cell Growth Processes
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Cerebral Cortex / metabolism
  • Dendritic Spines / metabolism*
  • Dendritic Spines / physiology
  • Mice
  • Wnt Signaling Pathway*
  • Wnt2 Protein / genetics
  • Wnt2 Protein / metabolism

Substances

  • Brain-Derived Neurotrophic Factor
  • Wnt2 Protein