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

Thomas Kerloch, Fanny Farrugia, Marlene Maitre, Geoffrey Terral, Muriel Koehl, Julian Ik-Tsen Heng, Mylene Blanchard, Helene Doat, Thierry Leste-Lasserre, Adeline Goron, Delphine Gonzales, Francois Guillemot, Nora Abrous, Emilie Pacary
Preprint bioRxiv. 2020-09-10; :
DOI: 10.1101/2020.09.10.290866

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 the 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 behaviour whereas its deletion in pups has no such effect, a finding supporting the adult neurogenesis hypothesis of anxiety disorders. Thus, our results provide mechanistic insight into the differential regulation of hippocampal neurogenesis during development and adulthood, and establishes a causal relationship between Rnd2 expression and anxiety.

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