The Reelin signaling pathway promotes dendritic spine development in hippocampal neurons

J Neurosci. 2008 Oct 8;28(41):10339-48. doi: 10.1523/JNEUROSCI.1917-08.2008.

Abstract

The development of distinct cellular layers and precise synaptic circuits is essential for the formation of well functioning cortical structures in the mammalian brain. The extracellular protein Reelin, through the activation of a core signaling pathway, including the receptors ApoER2 and VLDLR (very low density lipoprotein receptor) and the adapter protein Dab1 (Disabled-1), controls the positioning of radially migrating principal neurons, promotes the extension of dendritic processes in immature forebrain neurons, and affects synaptic transmission. Here we report for the first time that the Reelin signaling pathway promotes the development of postsynaptic structures such as dendritic spines in hippocampal pyramidal neurons. Our data underscore the importance of Reelin as a factor that promotes the maturation of target neuronal populations and the development of excitatory circuits in the postnatal hippocampus. These findings may have implications for understanding the origin of cognitive disorders associated with Reelin deficiency.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Adhesion Molecules, Neuronal / deficiency
  • Cell Adhesion Molecules, Neuronal / metabolism*
  • Cells, Cultured
  • Dendritic Spines / physiology*
  • Dendritic Spines / ultrastructure
  • Extracellular Matrix Proteins / deficiency
  • Extracellular Matrix Proteins / metabolism*
  • Hippocampus / cytology
  • Hippocampus / physiology*
  • Hippocampus / ultrastructure
  • LDL-Receptor Related Proteins
  • Mice
  • Nerve Tissue Proteins / deficiency
  • Nerve Tissue Proteins / metabolism*
  • Pyramidal Cells / physiology*
  • Pyramidal Cells / ultrastructure
  • Receptors, LDL / metabolism
  • Receptors, Lipoprotein / metabolism
  • Recombinant Proteins / metabolism
  • Reelin Protein
  • Serine Endopeptidases / deficiency
  • Serine Endopeptidases / metabolism*
  • Signal Transduction / physiology*
  • src-Family Kinases / metabolism

Substances

  • Cell Adhesion Molecules, Neuronal
  • Dab1 protein, mouse
  • Extracellular Matrix Proteins
  • LDL-Receptor Related Proteins
  • Nerve Tissue Proteins
  • Receptors, LDL
  • Receptors, Lipoprotein
  • Recombinant Proteins
  • Reelin Protein
  • VLDL receptor
  • low density lipoprotein receptor-related protein 8
  • src-Family Kinases
  • Reln protein, mouse
  • Serine Endopeptidases