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

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posted on 24.02.2022, 10:40 authored by Thomas Kerloch, Fanny Farrugia, Lou Bouit, Marlène Maître, Geoffrey Terral, Muriel Koehl, Pierre Mortessagne, Julian Ik-Tsen Heng, Mylène Blanchard, Hélène Doat, Thierry Leste-Lasserre, Adeline Goron, Delphine Gonzales, David Perrais, François Guillemot, Djoher Nora Abrous, Emilie Pacary
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.

Funding

Crick (Grant ID: 10089, Grant title: Guillemot FC001089)

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