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

非典型 Rho GTPase Rnd2 对成人齿状颗粒神经元发育和焦虑样行为至关重要,但对新生儿神经发生并不重要

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作者: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 #

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.

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