Multiple EphB receptor tyrosine kinases shape dendritic spines in the hippocampus

Mark Henkemeyer, Olga S. Itkis, Michelle Ngo, Peter W. Hickmott, Iryna M. Ethell

Research output: Contribution to journalArticle

213 Scopus citations

Abstract

Here, using a genetic approach, we dissect the roles of EphB receptor tyrosine kinases in dendritic spine development. Analysis of EphB1, EphB2, and EphB3 double and triple mutant mice lacking these receptors in different combinations indicates that all three, although to varying degrees, are involved in dendritic spine morphogenesis and synapse formation in the hippocampus. Hippocampal neurons lacking EphB expression fail to form dendritic spines in vitro and they develop abnormal spines in vivo. Defective spine formation in the mutants is associated with a drastic reduction in excitatory glutamatergic synapses and the clustering of NMDA and AMPA receptors. We show further that a kinase-defective, truncating mutation in EphB2 also results in abnormal spine development and that ephrin-B2-mediated activation of the EphB receptors accelerates dendritic spine development. These results indicate EphB receptor cell autonomous forward signaling is responsible for dendritic spine formation and synaptic maturation in hippocampal neurons.

Original languageEnglish (US)
Pages (from-to)1313-1326
Number of pages14
JournalJournal of Cell Biology
Volume163
Issue number6
DOIs
StatePublished - Dec 22 2003

Keywords

  • Dendritic spine morphogenesis
  • Hippocampal neuron
  • Post-synaptic
  • Receptor signaling
  • Synapse

ASJC Scopus subject areas

  • Cell Biology

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