Positive regulation of neocortical synapse formation by the Plexin-D1 receptor

Brain Res. 2015 Aug 7:1616:157-165. doi: 10.1016/j.brainres.2015.05.005. Epub 2015 May 11.

Abstract

Synapse formation is a critical process during neural development and is coordinated by multiple signals. Several lines of evidence implicate the Plexin-D1 receptor in synaptogenesis. Studies have shown that Plexin-D1 signaling is involved in synaptic specificity and synapse formation in spinal cord and striatum. Expression of Plexin-D1 and its principal neural ligand, Sema3E, by neocortical neurons is temporally and spatially regulated, reaching the highest level at the time of synaptogenesis in mice. In this study, we examined the function of Plexin-D1 in synapse formation by primary neocortical neurons in vitro. A novel, automated image analysis method was developed to quantitate synapse formation under baseline conditions and with manipulation of Plexin-D1 levels. shRNA and overexpression manipulations caused opposite changes, with reduction resulting in less synapse formation, an effect distinct from that reported in the striatum. The data indicate that Plexin-D1 operates in a cell context-specific fashion, mediating different synaptogenic outcomes depending upon neuron type.

Keywords: Image analysis; In vitro; Intracortical; Mouse; Synaptogenesis.

Publication types

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

MeSH terms

  • Animals
  • Cell Adhesion Molecules, Neuronal / genetics
  • Cell Adhesion Molecules, Neuronal / metabolism*
  • Disks Large Homolog 4 Protein
  • Embryo, Mammalian
  • Female
  • Gene Expression Regulation, Developmental / genetics*
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Guanylate Kinases / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Membrane Glycoproteins
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microscopy, Confocal
  • Neocortex / cytology*
  • Neurons / physiology*
  • Pregnancy
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Synapses / genetics
  • Synapses / physiology*
  • Synapsins / metabolism
  • Transfection

Substances

  • Cell Adhesion Molecules, Neuronal
  • Disks Large Homolog 4 Protein
  • Dlg4 protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • Membrane Glycoproteins
  • Membrane Proteins
  • PLXND1 protein, human
  • RNA, Small Interfering
  • Synapsins
  • Green Fluorescent Proteins
  • Guanylate Kinases