The atypical Rho GTPase Rnd2 is critical for dentate granule neuron development and anxiety-like behavior during adult but not neonatal neurogenesis

Mol Psychiatry. 2021 Dec;26(12):7280-7295. doi: 10.1038/s41380-021-01301-z. Epub 2021 Sep 24.

Abstract

Despite the central role of Rho GTPases in neuronal development, their functions in adult hippocampal neurogenesis remain poorly explored. Here, by using a retrovirus-based loss-of-function approach in vivo, we show that the atypical Rho GTPase Rnd2 is crucial for survival, positioning, somatodendritic morphogenesis, and functional maturation of adult-born dentate granule neurons. Interestingly, most of these functions are specific to granule neurons generated during adulthood since the deletion of Rnd2 in neonatally-born granule neurons only affects dendritogenesis. In addition, suppression of Rnd2 in adult-born dentate granule neurons increases anxiety-like behavior whereas its deletion in pups has no such effect, a finding supporting the adult neurogenesis hypothesis of anxiety disorders. Thus, our results are in line with the view that adult neurogenesis is not a simple continuation of earlier processes from development, and establish a causal relationship between Rnd2 expression and anxiety.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anxiety* / genetics
  • Dentate Gyrus* / metabolism
  • Mice
  • Neurogenesis*
  • Neurons / metabolism
  • rho GTP-Binding Proteins / genetics
  • rho GTP-Binding Proteins / metabolism*

Substances

  • Rnd2 protein, mouse
  • rho GTP-Binding Proteins