Rho family GTPases, Rac and Cdc42, control the localization of neonatal dentate granule cells during brain development

Hippocampus. 2019 Jul;29(7):569-578. doi: 10.1002/hipo.23047. Epub 2018 Nov 25.

Abstract

The hippocampus is generally considered as a brain center for learning and memory. We have recently established an electroporation-mediated gene transfer method to investigate the development of neonatal dentate granule cells in vivo. Using this new technique, we introduced knockdown vectors against Rac1 small GTPase into precursors for dentate granule cells at postnatal day 0. After 21 days, Rac1-deficient cells were frequently mispositioned between the granule cell layer (GCL) and hilus. About 60% of these mislocalized cells expressed a dentate granule cell marker, Prox1. Both the dendritic spine density and the ratio of mature spine were reduced when Rac1 was silenced. Notably, the deficient cells have immature thin processes during migrating in the early neonatal period. Knockdown of another Rac isoform, Rac3, also resulted in mislocalization of neonatally born dentate granule cells. In addition, knockdown of Cdc42, another Rho family protein, also caused mislocalization of the cell, although the effects were moderate compared to Rac1 and 3. Despite the ectopic localization, Rac3- or Cdc42-disrupted mispositioned cells expressed Prox1. These results indicate that Rho signaling pathways differentially regulate the proper localization and differentiation of dentate granule cells.

Keywords: Rho GTPase; dentate gyrus; hippocampus; neurogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Cell Differentiation
  • Cell Movement
  • Dentate Gyrus / cytology
  • Dentate Gyrus / enzymology*
  • Dentate Gyrus / growth & development*
  • Gene Knockdown Techniques
  • Gene Transfer Techniques
  • Homeodomain Proteins / metabolism
  • Mice
  • Mice, Inbred ICR
  • Neurogenesis
  • Neuropeptides / deficiency
  • Neuropeptides / genetics
  • Neuropeptides / metabolism*
  • RNA Interference
  • Signal Transduction
  • Tumor Suppressor Proteins / metabolism
  • cdc42 GTP-Binding Protein / deficiency
  • cdc42 GTP-Binding Protein / genetics
  • cdc42 GTP-Binding Protein / metabolism*
  • rac GTP-Binding Proteins / deficiency
  • rac GTP-Binding Proteins / genetics
  • rac GTP-Binding Proteins / metabolism*
  • rac1 GTP-Binding Protein / deficiency
  • rac1 GTP-Binding Protein / genetics
  • rac1 GTP-Binding Protein / metabolism*

Substances

  • Cdc42 protein, mouse
  • Homeodomain Proteins
  • Neuropeptides
  • Rac1 protein, mouse
  • Tumor Suppressor Proteins
  • prospero-related homeobox 1 protein
  • Rac3 protein, mouse
  • cdc42 GTP-Binding Protein
  • rac GTP-Binding Proteins
  • rac1 GTP-Binding Protein